Category Archives: Human Genetic Engineering

Genetic engineering in is founded on the idea of manipulating the gene pool in order to make lives better. One way of doing this is to start from the basic, from the egg cell and sperm cell. Another way is to swap bad genes in a fully formed human with good ones.

There are moral and ethical controversies surrounding genetic engineering or genetic mutation in humans. Personal convictions alone dictate people what to oppose and what to accept. However, it takes an objective inspection of this medical technology for us to draw a more acceptable conclusion and prevent pre-created biases.

1. Helps Prevent Genetic DisordersMany of the diseases today are hereditary or genetic. By manipulating the genes in humans, scientists find a way to prevent people from suffering from an otherwise hereditary health condition.

2. Helps Individual Have Better LifeGenetic engineering helps humans have a chance at a healthier, longer life with more desirable physical characteristics. By altering the genes of fetuses, there is a strong likelihood that future generations will be taller, stronger, healthier and better looking.

3. Helps Deepen Understanding of GenesPromoting genetic engineering is one way of deepening our understanding about human genetics. It helps scientists find ways to cure or prevent hereditary diseases, most especially.

4. Allows Parents to Choose Babys TraitsSome parents would want their children not to inherit their less desirable traits, if given the chance. By modifying the genes of babies, parents have a chance at designing their own babies, according to what they want gender, color of hair, etc.

5. Probes into Medical AdvancementsThere are many areas in science, which continue to be a mystery to even the most learned scientists and researchers today. Other advancements in the medical field can spring from genetic engineering.

1. Test Failure Leads to Termination of EmbryosSince genetic engineering is not a perfect science, and far from being so, there will be failures along the way, and this leads to termination of embryos with undesirable gene pool. To some people, this is tantamount to abortion.

2. Who Decides the Good and Bad GenesNo one has the right to decide or judge what specific traits are good or bad. With genetic engineering, the power likely rests on the scientists, the future parents, or the political leader. However, are these people accountable or responsible when experiments go wrong?

3. Engineered Babies Could Have Worse Imperfections When the actual results are not the outcome initially intended, society could have grave issues regarding the presence of erroneously engineered humans, specifically if they turn out to be mentally ill, psychotic, abusive, or non-responsive. How does society control these badly designed humans by murder, by further experimentation or by imprisonment?

4. It Is Very ExpensiveEngineering the genes of animals is already intricate and expensive enough, how much more an entire human being? It takes a team of skilled geneticists and researchers, plus a topnotch facility, to perform the experiment. This means that genetic engineering may only be available to the wealthy, furthering the gap in society.

5. Reduces the Individuality among HumansWhen there is a consensus as to which traits are good or bad, there is a tendency for future generations to lose their diversity and individuality. There will be no short people because being tall is more desirable. There will be no fat people because being slender is more desirable. Ultimately, the reduction of undesirable traits in humans would lead to a generation of pure breeds with very little capability of adapting to changes in the environment as in the case of pure breed animals, which are prone to disease.

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Genetic Engineering in Humans Pros and Cons List | NYLN.org

Genetic engineering is a term that was first introduced into our language in the 1970s to describe the emerging field of recombinant DNA technology and some of the things that were going on. As most people who read textbooks and things know, recombinant DNA technology started with pretty simple things--cloning very small pieces of DNA and growing them in bacteria--and has evolved to an enormous field where whole genomes can be cloned and moved from cell to cell, to cell using variations of techniques that all would come under genetic engineering as a very broad definition. To me, genetic engineering, broadly defined, means that you are taking pieces of DNA and combining them with other pieces of DNA. [This] doesn't really happen in nature, but is something that you engineer in your own laboratory and test tubes. And then taking what you have engineered and propagating that in any number of different organisms that range from bacterial cells to yeast cells, to plants and animals. So while there isn't a precise definition of genetic engineering, I think it more defines an entire field of recombinant DNA technology, genomics, and genetics in the 2000s.

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Genetic Engineering | Talking Glossary of Genetic Terms ...

Manipulation of genes in natural organisms, such as plants, animals, and even humans, is considered genetic engineering. This is done using a variety of different techniques like molecular cloning. These processes can cause dramatic changes in the natural makeup and characteristic of the organism. There are benefits and risks associated with genetic engineering, just like most other scientific practices.

Genetic engineering offers benefits such as:

1. Better Flavor, Growth Rate and NutritionCrops like potatoes, soybeans and tomatoes are now sometimes genetically engineered in order to improve size, crop yield, and nutritional values of the plants. These genetically engineered crops also possess the ability to grow in lands that would normally not be suitable for cultivation.

2. Pest-resistant Crops and Extended Shelf LifeEngineered seeds can resist pests and having a better chance at survival in harsh weather. Biotechnology could be in increasing the shelf life of many foods.

3. Genetic Alteration to Supply New FoodsGenetic engineering can also be used in producing completely new substances like proteins or other nutrients in food. This may up the benefits they have for medical uses.

4. Modification of the Human DNAGenes that are responsible for unique and desirable qualities in the human DNA can be exposed and introduced into the genes of another person. This changes the structural elements of a persons DNA. The effects of this are not know.

The following are the issues that genetic engineering can trigger:

1. May Hamper Nutritional ValueGenetic engineering on food also includes the infectivity of genes in root crops. These crops might supersede the natural weeds. These can be dangerous for the natural plants. Unpleasant genetic mutations could result to an increased allergy occurrence of the crop. Some people believe that this science on foods can hamper the nutrients contained by the crops although their appearance and taste were enhanced.

2. May Introduce Risky PathogensHorizontal gene shift could give increase to other pathogens. While it increases the immunity against diseases among the plants, the resistant genes can be transmitted to harmful pathogens.

3. May Result to Genetic ProblemsGene therapy on humans can end to some side effects. While relieving one problem, the treatment may cause the onset of another issue. As a single cell is liable for various characteristics, the cell isolation process will be responsible for one trait will be complicated.

4. Unfavorable to Genetic DiversityGenetic engineering can affect the diversity among the individuals. Cloning might be unfavorable to individualism. Furthermore, such process might not be affordable for poor. Hence, it makes the gene therapy impossible for an average person.

Genetic engineering might work excellently but after all, it is a kind of process that manipulates the natural. This is altering something which has not been created originally by humans. What can you say about this?

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Pros and Cons of Genetic Engineering - HRF

In April 2015, China shocked the world by with the announcement that they have engineered human embryos. Researchers from the Sun Yat-sen University in Guangzhou confirmed that they had modified the gene responsible for thalassaemia, a fatal blood disorder.

Led by Junjiu Huang, the research team fended off fears of eugenics by stating that the embryos used were non-viable. Meaning, they couldnt have developed into humans. The achievement was the first in the world.

Critics have warned that China is becoming the Wild West of genetic research. They called whats being done as a first step towards the creation of designer children and have called for a ban on the practice around the world.

The research of the team from the Sun Yat-sen University was reported in the journal Protein and Cell. Science journals Nature and Science didnt want to publish the study on grounds of ethics.

Human Genetics Alert Director Dr David King said that the news underlines the importance of an immediate global ban on the development of GM designer babies. He adds, It is critical that we avoid a eugenic future in which the rich can buy themselves a baby with built-in genetic advantages. It is entirely unnecessary since there are many ethical ways to avoid thalassaemia. This research is a classic example of scientific careerism assuring ones place in the history books even though the research is unnecessary and unethical.

The Sun Yat-sen University team used a gene-editing technique known as CRISPR/Cas9, discovered by MIT scientists. CRISPR works based on the fact that when bacteria attacks viruses, they hack away at part of their genetic code which results in dismembering the virus. The cut-away gene is then replaced or repaired by another molecule which is introduced at the same time. This technique has been used in adult cells and animal cells, but has never been tried on human embryos.

The team used embryos obtained from fertility clinics that were created for IVF use but had an extra set of chromosomes, a result that followed fertilization by two sperm, and prevents them from resulting in a live birth. The team injected 89 embryos with Cas9 protein. Of that, 71 survived and 54 were genetically tested. From that, 28 were spliced successfully and just a fraction of those had the replacement genetic material.

Dr Philippa Brice, from the health policy think-tank PHG Foundation, says of the news: This story underlines the urgent necessity for international dialogue over the ethics of germline editing in human embryos, well in advance of any progression towards theoretical clinical application. She adds, Recent calls for a moratorium on any such research to allow time for expert and public consideration of what is and is not ethically, socially and indeed legally acceptable with respect to human germline genetic modification should definitely be heeded.

Human genetic engineering is such a huge debate, with advocates and detractors. Lets look at the arguments of both sides of the divide:

1. It eliminates devastating inherited diseasesBirthing a child who is 100% healthy is a dream of every parent. However, that is not always the case. Theres a huge chance that a child ends up sickly as they grow older and sometimes carried over into adulthood. No parent wants to see their child suffer, and human genetic engineering seems to provide the answer to creating healthy and disease-free kids.

Also, if parents have a known family history of devastating illnesses, they know that that could be passed on to their offspring. In particular, if both parents have health issues to begin with, they are worried that might get passed on to their child. Again, its difficult for parents to deal with sickness in a child, especially if it leads to early death. And they want to do everything they can to ensure a healthy baby, and apparently, thats something the realm of human genetic engineering can provide.

2. It helps extend lifeImagine a world where people are born free from diseases. Surely, inhabitants of that world would be able to live longer and have healthier lives. Some of those who support the idea of modifying the human gene believe that it improves the quality of life.

3. It prevents the spread of disease to the next generationLets just say that a genetically modified human being produces an offspring. Given that genes are inherited, that child will get the traits their parents were made with. If their parents were made to have superior intellectual ability, then the child might inherit the same. In other words, its the beginning of a superior race something that isnt seen too kindly by everyone given our own history regarding that matter.

1. It crosses the ethical lineWith genetic engineering, the physical appearance, metabolism of future children can be changed. In fact, even their physical capabilities and mental faculties (including memory and intelligence) can be improved upon. Ethical concerns regarding germline engineering are in the lines of every fetus has the right to remain genetically unmodified.

2. It raises safety issuesWith cloning animals, it has been shown that there are certain health issues involved. While Dolly the Sheep did live to see more than five years, she also had a couple of health scares that shortened her life. The animals cloned after Dolly didnt fare well either, even the extinct specie of mountain goat only lived for a couple of minutes.

The same can be said with modifying human genes. Although the Chinese study mentioned here reported successful results, the actual consequences of creating life through modification isnt yet known. That and the fact that the process of modifying genes is rather complex, the success rate is something of concern.

While other would want to conduct further studies on this, the topic is one that is frowned upon by a majority around the world. Also, there are rules and laws in place that prohibit the practice of genetically modifying humans.

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5 Standout Pros and Cons of Human Genetic Engineering ...

Genetic Engineering and Animals: A Short Summary of the Legal Terrain and Ethical ImplicationsAndrew B. Perzigian (2003)

With the advent and rapid development of genetic engineering technology, the animal rights movement is currently facing one of its greatest challenges and dilemmas. Proponents of the technology assert that transgenic animals, animals that have been genetically altered through the introduction of another plant's or animal's genes, may one day help solve many of our modern day problems in life, from starvation and ill health, to environmental degradation and the modern extinction crisis. Critics believe that bioengineering poses greater risks than it does benefits. They argue that genetic engineering threatens to increase animal suffering and decrease species integrity, while at the same time creating a potentially devastating impact on the balance and sustainability of the Earth's ecosystem. Regardless, the value judgments we make regarding the direction and scope that this technology should take are sure to have far reaching implications.

Transgenic animals are animals that have, through genetic engineering, genes from other plants and animals. Unlike controlled breeding, which is confined to the genetic material contained in a single species, modern genetic engineering permits an almost limitless scope of modification and introduction of otherwise foreign genetic material. This permits specific traits, and not the host of other traits common from crossbreeding, to be effectively introduced into new, transgenic animal species. Genetic engineering is able to create whole organisms that are not natural to the planet, and whose specific genetic make-up is as much a result of human manipulation as it is natural selection. (For further information on the basics of genetic engineering, see Detailed Discussion ).

With regard to the agricultural industry, transgenic farm animals can be created, that are better able to resist disease, grow faster, and more efficiently reproduce than current species of animals. Transgenic sheep can be created to produce better wool and cows can be engineered to more efficiently convert grain into higher quality milk and meat. Transgenic salmon, salmon that grow larger and at a faster rate than natural varieties, have already been created and farmed. (For further information on thepotential benefits, see Detailed Discussion ).

One of the more controversial uses of this technology is found in recent proposals to engineer farm animals to be non-sentient, without the "stress" genes that cause them great suffering during their lives on industrial factory farms. Since sentience, the ability to feel pain and experience suffering, is the basis upon which much animal rights ideology is based, some argue that these types of transgenic farm animals would help to solve many of the animal welfare issues posed by industrial factory farms. (For more information on the risks, see Detailed Discussion ).

The bio-medical research industry has been equally influenced by genetic engineering technology. Instead of relying on numerous test animals to research modern diseases and appropriate drug therapies, the bio-medical community can now rely on specifically engineered animal research models. Such animals are bred to have an increase susceptibility to modern diseases, like hereditary breast cancer. Transgenic animals have made research of such diseases more accurate, less expensive and faster, while at the same time permitting accurate results with the use of fewer individual animals in any given study.

Also, transgenic animals, like goats, sheep, and cattle, have been engineered to produce large amounts of complex human proteins in their milk, something very useful in the creation of therapeutic drugs. By engineering these animals to release these and other proteins in their milk, the mass production of high quality therapeutic drugs is made less costly, easier to manufacture, and at the expense of fewer animal lives than what was formerly the case. (For more information on the scientific andmedical potential of genetic engineering, see DetailedDiscussion ).

Biotechnology breakthroughs in whole animal cloning have led to many suggestions that such technology could be used to clone endangered species. Cloning provides a great support blanket for the modern extinction crisis and can help to ensure that critical numbers of endangered species will exist for generations to come.

In general, opponents of genetic engineering assert that such technology creates a huge diminution in the standing of animals, leaving them as nothing more than "test tubes with tails," only of benefit for the exploitive practices of factory farming, and drug and organ manufacturing. Creating more efficient agricultural animals threatens weaken the genetic diversity of the herd and thereby make them more susceptible to new strains of infectious disease. Also, if transgenic farm animals ever escape into wild populations, they can have profoundly disturbing effects on the natural environment, including a complete elimination of natural populations and the processes of natural selection.

Animal rights advocates also argue that each species should enjoy an inherent, natural right to be free of genetic manipulation in any form. This is especially the case when genetic engineering is used as a means of depriving animals of their sentience, of exacerbating the cruel, horrific conditions of the modern factory farm and biomedical lab. Although the sheer numbers may decline, the actual suffering experienced by agricultural and research animals may increase.

Cloning endangered species, although useful as a last resort, may unwisely shift our efforts away from protecting the critical habitat necessary to sustain viable endangered species populations. Habitat protection is as important to saving endangered species as is the specific renewal and maintenance of viable numbers within a population. Since limited funds exist, habitat protection, and not expensive cloning technology, should be the focus of our endangered species protection efforts. (For more information on the inherent dangers, see Detailed Discussion ).

Currently, there are few laws, in either the United States or the European Union (EU) regulating animal cloning and the creation of transgenic animals. In the United States, most research and farm animals are excluded from federal protection. While the European Union (EU) ensures that such animals are treated more humanely than is the case in the United States, both the U.S. and the EU extend patent protection to the owners and creators of transgenic animal species. This provides a huge incentive for the biotechnology industry to continually research and develop novel transgenic animal creations. With patents, researchers can now own and monopolize entire animal species, something unheard of prior to modern genetic engineering. The Supreme Court has upheld transgenic animal patents without any review of the potential ethical and environmental risks associated with the technology involved. (For moreon this important decision, click here ).

Most modern legislation regarding genetic engineering and cloning technology ensued following the birth of Dolly the sheep, the first multi-cellular organism cloned from adult cells. The primary objectives of the subsequent United States and EU legislation was to ban human cloning while at the same time ensuring that genetic engineering research continued unimpeded by such legislation. Patent protection effectively promotes genetic engineering research and helps to ensure its speedy development. (For more information on U.S. and European laws concerning biotechnology, see Detailed Discussion ).

There is no doubt that genetic engineering of animals will continue well into the future. Both the United States' and the EU's legal systems have been slow to respond with legislation specifically regulating biotechnology, and each have permitted their patent law to provide a supportive ground for genetic engineering research and development. One thing is for sure, we must not sit complacently by as this technology rapidly changes the fabric of our existence from the inside out. We must not wait and see what the effects are. We must form educated opinions, inspire legislative regulation, and hope that whatever direction that bioengineering takes us, is a positive step towards decreased animal suffering, increased environmental sustainability, and an overall compassionate regard for the earth and its precious life.

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Genetic Engineering and Animals | Animal Legal ...

The human genome is the complete set of nucleic acid sequences for humans, encoded as DNA within the 23 chromosome pairs in cell nuclei and in a small DNA molecule found within individual mitochondria. These are usually treated separately as the nuclear genome, and the mitochondrial genome.[1] Human genomes include both protein-coding DNA genes and noncoding DNA. Haploid human genomes, which are contained in germ cells (the egg and sperm gamete cells created in the meiosis phase of sexual reproduction before fertilization creates a zygote) consist of three billion DNA base pairs, while diploid genomes (found in somatic cells) have twice the DNA content. While there are significant differences among the genomes of human individuals (on the order of 0.1%),[2] these are considerably smaller than the differences between humans and their closest living relatives, the chimpanzees (approximately 4%[3]) and bonobos.

The first human genome sequences were published in nearly complete draft form in February 2001 by the Human Genome Project[4] and Celera Corporation.[5] Completion of the Human Genome Project Sequence was published in 2004.[6] The human genome was the first of all vertebrates to be completely sequenced. As of 2012, thousands of human genomes have been completely sequenced, and many more have been mapped at lower levels of resolution. This data is used worldwide in biomedical science, anthropology, forensics and other branches of science. There is a widely held expectation that genomic studies will lead to advances in the diagnosis and treatment of diseases, and to new insights in many fields of biology, including human evolution.

Although the sequence of the human genome has been (almost) completely determined by DNA sequencing, it is not yet fully understood. Most (though probably not all) genes have been identified by a combination of high throughput experimental and bioinformatics approaches, yet much work still needs to be done to further elucidate the biological functions of their protein and RNA products. Recent results suggest that most of the vast quantities of noncoding DNA within the genome have associated biochemical activities, including regulation of gene expression, organization of chromosome architecture, and signals controlling epigenetic inheritance.

There are an estimated 19,000-20,000 human protein-coding genes.[7] The estimate of the number of human genes has been repeatedly revised down from initial predictions of 100,000 or more as genome sequence quality and gene finding methods have improved, and could continue to drop further.[6][8] Protein-coding sequences account for only a very small fraction of the genome (approximately 1.5%), and the rest is associated with non-coding RNA molecules, regulatory DNA sequences, LINEs, SINEs, introns, and sequences for which as yet no function has been determined.[9]

In June 2016, scientists formally announced HGP-Write, a plan to synthesize the human genome.[10][11]

The total length of the human genome is over 3 billion base pairs. The genome is organized into 22 paired chromosomes, plus the X chromosome (one in males, two in females) and, in males only, one Y chromosome. These are all large linear DNA molecules contained within the cell nucleus. The genome also includes the mitochondrial DNA, a comparatively small circular molecule present in each mitochondrion. Basic information about these molecules and their gene content, based on a reference genome that does not represent the sequence of any specific individual, are provided in the following table. (Data source: Ensembl genome browser release 87, December 2016 for most values; Ensembl genome browser release 68, July 2012 for miRNA, rRNA, snRNA, snoRNA.)

Table 1 (above) summarizes the physical organization and gene content of the human reference genome, with links to the original analysis, as published in the Ensembl database at the European Bioinformatics Institute (EBI) and Wellcome Trust Sanger Institute. Chromosome lengths were estimated by multiplying the number of base pairs by 0.34 nanometers, the distance between base pairs in the DNA double helix. A recent estimation of human chromosome lengths based on updated data reports 205.00 cm for the diploid male genome and 208.23 cm for female, corresponding to weights of 6.41 and 6.51 picograms (pg), respectively.[12] The number of proteins is based on the number of initial precursor mRNA transcripts, and does not include products of alternative pre-mRNA splicing, or modifications to protein structure that occur after translation.

Variations are unique DNA sequence differences that have been identified in the individual human genome sequences analyzed by Ensembl as of December, 2016. The number of identified variations is expected to increase as further personal genomes are sequenced and analyzed. In addition to the gene content shown in this table, a large number of non-expressed functional sequences have been identified throughout the human genome (see below). Links open windows to the reference chromosome sequences in the EBI genome browser.

Small non-coding RNAs are RNAs of as many as 200 bases that do not have protein-coding potential. These include: microRNAs, or miRNAs (post-transcriptional regulators of gene expression), small nuclear RNAs, or snRNAs (the RNA components of spliceosomes), and small nucleolar RNAs, or snoRNA (involved in guiding chemical modifications to other RNA molecules). Long non-coding RNAs are RNA molecules longer than 200 bases that do not have protein-coding potential. These include: ribosomal RNAs, or rRNAs (the RNA components of ribosomes), and a variety of other long RNAs that are involved in regulation of gene expression, epigenetic modifications of DNA nucleotides and histone proteins, and regulation of the activity of protein-coding genes. Small discrepancies between total-small-ncRNA numbers and the numbers of specific types of small ncNRAs result from the former values being sourced from Ensembl release 87 and the latter from Ensembl release 68.

Although the human genome has been completely sequenced for all practical purposes, there are still hundreds of gaps in the sequence. A recent study noted more than 160 euchromatic gaps of which 50 gaps were closed.[13] However, there are still numerous gaps in the heterochromatic parts of the genome which is much harder to sequence due to numerous repeats and other intractable sequence features.

The human reference genome (GRC v38) has been successfully compressed to ~5.2-fold (marginally less than 550 MB) in 155 minutes using a desktop computer with 6.4 GB of RAM.[14]

The haploid human genome (23 chromosomes) is about 3 billion base pairs long and contains around 30,000 genes.[15] Since every base pair can be coded by 2 bits, this is about 750 megabytes of data. An individual somatic (diploid) cell contains twice this amount, that is, about 6 billion base pairs. Men have fewer than women because the Y chromosome is about 57 million base pairs whereas the X is about 156 million, but in terms of information men have more because the second X contains almost the same information as the first[citation needed]. Since individual genomes vary in sequence by less than 1% from each other, the variations of a given human's genome from a common reference can be losslessly compressed to roughly 4 megabytes.[16]

The entropy rate of the genome differs significantly between coding and non-coding sequences. It is close to the maximum of 2 bits per base pair for the coding sequences (about 45 million base pairs), but less for the non-coding parts. It ranges between 1.5 and 1.9 bits per base pair for the individual chromosome, except for the Y-chromosome, which has an entropy rate below 0.9 bits per base pair.[17]

The content of the human genome is commonly divided into coding and noncoding DNA sequences. Coding DNA is defined as those sequences that can be transcribed into mRNA and translated into proteins during the human life cycle; these sequences occupy only a small fraction of the genome (<2%). Noncoding DNA is made up of all of those sequences (ca. 98% of the genome) that are not used to encode proteins.

Some noncoding DNA contains genes for RNA molecules with important biological functions (noncoding RNA, for example ribosomal RNA and transfer RNA). The exploration of the function and evolutionary origin of noncoding DNA is an important goal of contemporary genome research, including the ENCODE (Encyclopedia of DNA Elements) project, which aims to survey the entire human genome, using a variety of experimental tools whose results are indicative of molecular activity.

Because non-coding DNA greatly outnumbers coding DNA, the concept of the sequenced genome has become a more focused analytical concept than the classical concept of the DNA-coding gene.[18][19]

Protein-coding sequences represent the most widely studied and best understood component of the human genome. These sequences ultimately lead to the production of all human proteins, although several biological processes (e.g. DNA rearrangements and alternative pre-mRNA splicing) can lead to the production of many more unique proteins than the number of protein-coding genes.

The complete modular protein-coding capacity of the genome is contained within the exome, and consists of DNA sequences encoded by exons that can be translated into proteins. Because of its biological importance, and the fact that it constitutes less than 2% of the genome, sequencing of the exome was the first major milepost of the Human Genome Project.

Number of protein-coding genes. About 20,000 human proteins have been annotated in databases such as Uniprot.[21] Historically, estimates for the number of protein genes have varied widely, ranging up to 2,000,000 in the late 1960s,[22] but several researchers pointed out in the early 1970s that the estimated mutational load from deleterious mutations placed an upper limit of approximately 40,000 for the total number of functional loci (this includes protein-coding and functional non-coding genes).[23]

The number of human protein-coding genes is not significantly larger than that of many less complex organisms, such as the roundworm and the fruit fly. This difference may result from the extensive use of alternative pre-mRNA splicing in humans, which provides the ability to build a very large number of modular proteins through the selective incorporation of exons.

Protein-coding capacity per chromosome. Protein-coding genes are distributed unevenly across the chromosomes, ranging from a few dozen to more than 2000, with an especially high gene density within chromosomes 19, 11, and 1 (Table 1). Each chromosome contains various gene-rich and gene-poor regions, which may be correlated with chromosome bands and GC-content.[24] The significance of these nonrandom patterns of gene density is not well understood[25]

Size of protein-coding genes. The size of protein-coding genes within the human genome shows enormous variability (Table 2). The median size of a protein-coding gene is 26,288 bp (mean = 66,577 bp; Table 2 in [26]). For example, the gene for histone H1a (HIST1HIA) is relatively small and simple, lacking introns and encoding mRNA sequences of 781 nt and a 215 amino acid protein (648 nt open reading frame). Dystrophin (DMD) is the largest protein-coding gene in the human reference genome, spanning a total of 2.2 MB, while Titin (TTN) has the longest coding sequence (114,414 bp), the largest number of exons (363),[27] and the longest single exon (17,106 bp). Over the whole genome, the median size of an exon is 122 bp (mean = 145 bp), the median number of exons is 7 (mean = 8.8), and the median coding sequence encodes 367 amino acids (mean = 447 amino acids; Table 21 in[9] ).

Table 2. Examples of human protein-coding genes. Chrom, chromosome. Alt splicing, alternative pre-mRNA splicing. (Data source: Ensembl genome browser release 68, July 2012)

Recently, a systematic meta-analysis of updated data of the human genome [26] found that the largest protein-coding gene in the human reference genome is RBFOX1 (RNA binding protein, fox-1 homolog 1), spanning a total of 2.47 MB. Over the whole genome, considering a curated set of protein-coding genes, the median size of an exon is currently estimated to be 133 bp (mean = 309 bp), the median number of exons is currently estimated to be 8 (mean = 11), and the median coding sequence is currently estimated to encode 425 amino acids (mean = 553 amino acids; Tables 2 and 5 in[26]).

Noncoding DNA is defined as all of the DNA sequences within a genome that are not found within protein-coding exons, and so are never represented within the amino acid sequence of expressed proteins. By this definition, more than 98% of the human genomes is composed of ncDNA.

Numerous classes of noncoding DNA have been identified, including genes for noncoding RNA (e.g. tRNA and rRNA), pseudogenes, introns, untranslated regions of mRNA, regulatory DNA sequences, repetitive DNA sequences, and sequences related to mobile genetic elements.

Numerous sequences that are included within genes are also defined as noncoding DNA. These include genes for noncoding RNA (e.g. tRNA, rRNA), and untranslated components of protein-coding genes (e.g. introns, and 5' and 3' untranslated regions of mRNA).

Protein-coding sequences (specifically, coding exons) constitute less than 1.5% of the human genome.[9] In addition, about 26% of the human genome is introns.[28] Aside from genes (exons and introns) and known regulatory sequences (820%), the human genome contains regions of noncoding DNA. The exact amount of noncoding DNA that plays a role in cell physiology has been hotly debated. Recent analysis by the ENCODE project indicates that 80% of the entire human genome is either transcribed, binds to regulatory proteins, or is associated with some other biochemical activity.[8]

It however remains controversial whether all of this biochemical activity contributes to cell physiology, or whether a substantial portion of this is the result transcriptional and biochemical noise, which must be actively filtered out by the organism.[29] Excluding protein-coding sequences, introns, and regulatory regions, much of the non-coding DNA is composed of:Many DNA sequences that do not play a role in gene expression have important biological functions. Comparative genomics studies indicate that about 5% of the genome contains sequences of noncoding DNA that are highly conserved, sometimes on time-scales representing hundreds of millions of years, implying that these noncoding regions are under strong evolutionary pressure and positive selection.[30]

Many of these sequences regulate the structure of chromosomes by limiting the regions of heterochromatin formation and regulating structural features of the chromosomes, such as the telomeres and centromeres. Other noncoding regions serve as origins of DNA replication. Finally several regions are transcribed into functional noncoding RNA that regulate the expression of protein-coding genes (for example[31] ), mRNA translation and stability (see miRNA), chromatin structure (including histone modifications, for example[32] ), DNA methylation (for example[33] ), DNA recombination (for example[34] ), and cross-regulate other noncoding RNAs (for example[35] ). It is also likely that many transcribed noncoding regions do not serve any role and that this transcription is the product of non-specific RNA Polymerase activity.[29]

Pseudogenes are inactive copies of protein-coding genes, often generated by gene duplication, that have become nonfunctional through the accumulation of inactivating mutations. Table 1 shows that the number of pseudogenes in the human genome is on the order of 13,000,[36] and in some chromosomes is nearly the same as the number of functional protein-coding genes. Gene duplication is a major mechanism through which new genetic material is generated during molecular evolution.

For example, the olfactory receptor gene family is one of the best-documented examples of pseudogenes in the human genome. More than 60 percent of the genes in this family are non-functional pseudogenes in humans. By comparison, only 20 percent of genes in the mouse olfactory receptor gene family are pseudogenes. Research suggests that this is a species-specific characteristic, as the most closely related primates all have proportionally fewer pseudogenes. This genetic discovery helps to explain the less acute sense of smell in humans relative to other mammals.[37]

Noncoding RNA molecules play many essential roles in cells, especially in the many reactions of protein synthesis and RNA processing. Noncoding RNA include tRNA, ribosomal RNA, microRNA, snRNA and other non-coding RNA genes including about 60,000 long non coding RNAs (lncRNAs).[8][38][39][40] Although the number of reported lncRNA genes continues to rise and the exact number in the human genome is yet to be defined, many of them are argued to be non-functional.[41]

Many ncRNAs are critical elements in gene regulation and expression. Noncoding RNA also contributes to epigenetics, transcription, RNA splicing, and the translational machinery. The role of RNA in genetic regulation and disease offers a new potential level of unexplored genomic complexity.[42]

In addition to the ncRNA molecules that are encoded by discrete genes, the initial transcripts of protein coding genes usually contain extensive noncoding sequences, in the form of introns, 5'-untranslated regions (5'-UTR), and 3'-untranslated regions (3'-UTR). Within most protein-coding genes of the human genome, the length of intron sequences is 10- to 100-times the length of exon sequences (Table 2).

The human genome has many different regulatory sequences which are crucial to controlling gene expression. Conservative estimates indicate that these sequences make up 8% of the genome,[43] however extrapolations from the ENCODE project give that 20[44]-40%[45] of the genome is gene regulatory sequence. Some types of non-coding DNA are genetic "switches" that do not encode proteins, but do regulate when and where genes are expressed (called enhancers).[46]

Regulatory sequences have been known since the late 1960s.[47] The first identification of regulatory sequences in the human genome relied on recombinant DNA technology.[48] Later with the advent of genomic sequencing, the identification of these sequences could be inferred by evolutionary conservation. The evolutionary branch between the primates and mouse, for example, occurred 7090 million years ago.[49] So computer comparisons of gene sequences that identify conserved non-coding sequences will be an indication of their importance in duties such as gene regulation.[50]

Other genomes have been sequenced with the same intention of aiding conservation-guided methods, for exampled the pufferfish genome.[51] However, regulatory sequences disappear and re-evolve during evolution at a high rate.[52][53][54]

As of 2012, the efforts have shifted toward finding interactions between DNA and regulatory proteins by the technique ChIP-Seq, or gaps where the DNA is not packaged by histones (DNase hypersensitive sites), both of which tell where there are active regulatory sequences in the investigated cell type.[43]

Repetitive DNA sequences comprise approximately 50% of the human genome.[55]

About 8% of the human genome consists of tandem DNA arrays or tandem repeats, low complexity repeat sequences that have multiple adjacent copies (e.g. "CAGCAGCAG...").[56]The tandem sequences may be of variable lengths, from two nucleotides to tens of nucleotides. These sequences are highly variable, even among closely related individuals, and so are used for genealogical DNA testing and forensic DNA analysis.[57]

Repeated sequences of fewer than ten nucleotides (e.g. the dinucleotide repeat (AC)n) are termed microsatellite sequences. Among the microsatellite sequences, trinucleotide repeats are of particular importance, as sometimes occur within coding regions of genes for proteins and may lead to genetic disorders. For example, Huntington's disease results from an expansion of the trinucleotide repeat (CAG)n within the Huntingtin gene on human chromosome 4. Telomeres (the ends of linear chromosomes) end with a microsatellite hexanucleotide repeat of the sequence (TTAGGG)n.

Tandem repeats of longer sequences (arrays of repeated sequences 1060 nucleotides long) are termed minisatellites.

Transposable genetic elements, DNA sequences that can replicate and insert copies of themselves at other locations within a host genome, are an abundant component in the human genome. The most abundant transposon lineage, Alu, has about 50,000 active copies,[58] and can be inserted into intragenic and intergenic regions.[59] One other lineage, LINE-1, has about 100 active copies per genome (the number varies between people).[60] Together with non-functional relics of old transposons, they account for over half of total human DNA.[61] Sometimes called "jumping genes", transposons have played a major role in sculpting the human genome. Some of these sequences represent endogenous retroviruses, DNA copies of viral sequences that have become permanently integrated into the genome and are now passed on to succeeding generations.

Mobile elements within the human genome can be classified into LTR retrotransposons (8.3% of total genome), SINEs (13.1% of total genome) including Alu elements, LINEs (20.4% of total genome), SVAs and Class II DNA transposons (2.9% of total genome).

With the exception of identical twins, all humans show significant variation in genomic DNA sequences. The human reference genome (HRG) is used as a standard sequence reference.

There are several important points concerning the human reference genome:

The Genome Reference Consortium is responsible for updating the HRG. Version 38 was released in December 2013.[62]

Most studies of human genetic variation have focused on single-nucleotide polymorphisms (SNPs), which are substitutions in individual bases along a chromosome. Most analyses estimate that SNPs occur 1 in 1000 base pairs, on average, in the euchromatic human genome, although they do not occur at a uniform density. Thus follows the popular statement that "we are all, regardless of race, genetically 99.9% the same",[63] although this would be somewhat qualified by most geneticists. For example, a much larger fraction of the genome is now thought to be involved in copy number variation.[64] A large-scale collaborative effort to catalog SNP variations in the human genome is being undertaken by the International HapMap Project.

The genomic loci and length of certain types of small repetitive sequences are highly variable from person to person, which is the basis of DNA fingerprinting and DNA paternity testing technologies. The heterochromatic portions of the human genome, which total several hundred million base pairs, are also thought to be quite variable within the human population (they are so repetitive and so long that they cannot be accurately sequenced with current technology). These regions contain few genes, and it is unclear whether any significant phenotypic effect results from typical variation in repeats or heterochromatin.

Most gross genomic mutations in gamete germ cells probably result in inviable embryos; however, a number of human diseases are related to large-scale genomic abnormalities. Down syndrome, Turner Syndrome, and a number of other diseases result from nondisjunction of entire chromosomes. Cancer cells frequently have aneuploidy of chromosomes and chromosome arms, although a cause and effect relationship between aneuploidy and cancer has not been established.

Whereas a genome sequence lists the order of every DNA base in a genome, a genome map identifies the landmarks. A genome map is less detailed than a genome sequence and aids in navigating around the genome.[65][66]

An example of a variation map is the HapMap being developed by the International HapMap Project. The HapMap is a haplotype map of the human genome, "which will describe the common patterns of human DNA sequence variation."[67] It catalogs the patterns of small-scale variations in the genome that involve single DNA letters, or bases.

Researchers published the first sequence-based map of large-scale structural variation across the human genome in the journal Nature in May 2008.[68][69] Large-scale structural variations are differences in the genome among people that range from a few thousand to a few million DNA bases; some are gains or losses of stretches of genome sequence and others appear as re-arrangements of stretches of sequence. These variations include differences in the number of copies individuals have of a particular gene, deletions, translocations and inversions.

Single-nucleotide polymorphisms (SNPs) do not occur homogeneously across the human genome. In fact, there is enormous diversity in SNP frequency between genes, reflecting different selective pressures on each gene as well as different mutation and recombination rates across the genome. However, studies on SNPs are biased towards coding regions, the data generated from them are unlikely to reflect the overall distribution of SNPs throughout the genome. Therefore, the SNP Consortium protocol was designed to identify SNPs with no bias towards coding regions and the Consortium's 100,000 SNPs generally reflect sequence diversity across the human chromosomes.The SNP Consortium aims to expand the number of SNPs identified across the genome to 300 000 by the end of the first quarter of 2001.[70]

Changes in non-coding sequence and synonymous changes in coding sequence are generally more common than non-synonymous changes, reflecting greater selective pressure reducing diversity at positions dictating amino acid identity. Transitional changes are more common than transversions, with CpG dinucleotides showing the highest mutation rate, presumably due to deamination.

A personal genome sequence is a (nearly) complete sequence of the chemical base pairs that make up the DNA of a single person. Because medical treatments have different effects on different people due to genetic variations such as single-nucleotide polymorphisms (SNPs), the analysis of personal genomes may lead to personalized medical treatment based on individual genotypes.[71]

The first personal genome sequence to be determined was that of Craig Venter in 2007. Personal genomes had not been sequenced in the public Human Genome Project to protect the identity of volunteers who provided DNA samples. That sequence was derived from the DNA of several volunteers from a diverse population.[72] However, early in the Venter-led Celera Genomics genome sequencing effort the decision was made to switch from sequencing a composite sample to using DNA from a single individual, later revealed to have been Venter himself. Thus the Celera human genome sequence released in 2000 was largely that of one man. Subsequent replacement of the early composite-derived data and determination of the diploid sequence, representing both sets of chromosomes, rather than a haploid sequence originally reported, allowed the release of the first personal genome.[73] In April 2008, that of James Watson was also completed. Since then hundreds of personal genome sequences have been released,[74] including those of Desmond Tutu,[75][76] and of a Paleo-Eskimo.[77] In November 2013, a Spanish family made their personal genomics data publicly available under a Creative Commons public domain license. The work was led by Manuel Corpas and the data obtained by direct-to-consumer genetic testing with 23andMe and the Beijing Genomics Institute). This is believed to be the first such public genomics dataset for a whole family.[78]

The sequencing of individual genomes further unveiled levels of genetic complexity that had not been appreciated before. Personal genomics helped reveal the significant level of diversity in the human genome attributed not only to SNPs but structural variations as well. However, the application of such knowledge to the treatment of disease and in the medical field is only in its very beginnings.[79] Exome sequencing has become increasingly popular as a tool to aid in diagnosis of genetic disease because the exome contributes only 1% of the genomic sequence but accounts for roughly 85% of mutations that contribute significantly to disease.[80]

In humans, gene knockouts naturally occur as heterozygous or homozygous loss-of-function gene knockouts. These knockouts are often difficult to distinguish, especially within heterogeneous genetic backgrounds. They are also difficult to find as they occur in low frequencies.

Populations with high rates of consanguinity, such as countries with high rates of first-cousin marriages, display the highest frequencies of homozygous gene knockouts. Such populations include Pakistan, Iceland, and Amish populations. These populations with a high level of parental-relatedness have been subjects of human knock out research which has helped to determine the function of specific genes in humans. By distinguishing specific knockouts, researchers are able to use phenotypic analyses of these individuals to help characterize the gene that has been knocked out.

Knockouts in specific genes can cause genetic diseases, potentially have beneficial effects, or even result in no phenotypic effect at all. However, determining a knockouts phenotypic effect and in humans can be challenging. Challenges to characterizing and clinically interpreting knockouts include difficulty calling of DNA variants, determining disruption of protein function (annotation), and considering the amount of influence mosaicism has on the phenotype. [82]

One major study that investigated human knockouts is the Pakistan Risk of Myocardial Infarction study. It was found that individuals possessing a heterozygous loss-of-function gene knockout for the APOC3 gene had lower triglycerides in the blood after consuming a high fat meal as compared to individuals without the mutation. However, individuals possessing homozygous loss-of-function gene knockouts of the APOC3 gene displayed the lowest level of triglycerides in the blood after the fat load test, as they produce no functional APOC3 protein. [83]

Most aspects of human biology involve both genetic (inherited) and non-genetic (environmental) factors. Some inherited variation influences aspects of our biology that are not medical in nature (height, eye color, ability to taste or smell certain compounds, etc.). Moreover, some genetic disorders only cause disease in combination with the appropriate environmental factors (such as diet). With these caveats, genetic disorders may be described as clinically defined diseases caused by genomic DNA sequence variation. In the most straightforward cases, the disorder can be associated with variation in a single gene. For example, cystic fibrosis is caused by mutations in the CFTR gene, and is the most common recessive disorder in caucasian populations with over 1,300 different mutations known.[84]

Disease-causing mutations in specific genes are usually severe in terms of gene function, and are fortunately rare, thus genetic disorders are similarly individually rare. However, since there are many genes that can vary to cause genetic disorders, in aggregate they constitute a significant component of known medical conditions, especially in pediatric medicine. Molecularly characterized genetic disorders are those for which the underlying causal gene has been identified, currently there are approximately 2,200 such disorders annotated in the OMIM database.[84]

Studies of genetic disorders are often performed by means of family-based studies. In some instances population based approaches are employed, particularly in the case of so-called founder populations such as those in Finland, French-Canada, Utah, Sardinia, etc. Diagnosis and treatment of genetic disorders are usually performed by a geneticist-physician trained in clinical/medical genetics. The results of the Human Genome Project are likely to provide increased availability of genetic testing for gene-related disorders, and eventually improved treatment. Parents can be screened for hereditary conditions and counselled on the consequences, the probability it will be inherited, and how to avoid or ameliorate it in their offspring.

As noted above, there are many different kinds of DNA sequence variation, ranging from complete extra or missing chromosomes down to single nucleotide changes. It is generally presumed that much naturally occurring genetic variation in human populations is phenotypically neutral, i.e. has little or no detectable effect on the physiology of the individual (although there may be fractional differences in fitness defined over evolutionary time frames). Genetic disorders can be caused by any or all known types of sequence variation. To molecularly characterize a new genetic disorder, it is necessary to establish a causal link between a particular genomic sequence variant and the clinical disease under investigation. Such studies constitute the realm of human molecular genetics.

With the advent of the Human Genome and International HapMap Project, it has become feasible to explore subtle genetic influences on many common disease conditions such as diabetes, asthma, migraine, schizophrenia, etc. Although some causal links have been made between genomic sequence variants in particular genes and some of these diseases, often with much publicity in the general media, these are usually not considered to be genetic disorders per se as their causes are complex, involving many different genetic and environmental factors. Thus there may be disagreement in particular cases whether a specific medical condition should be termed a genetic disorder. The categorized table below provides the prevalence as well as the genes or chromosomes associated with some human genetic disorders.

Human development over the last 10 million years

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Comparative genomics studies of mammalian genomes suggest that approximately 5% of the human genome has been conserved by evolution since the divergence of extant lineages approximately 200 million years ago, containing the vast majority of genes.[86][87] The published chimpanzee genome differs from that of the human genome by 1.23% in direct sequence comparisons.[88] Around 20% of this figure is accounted for by variation within each species, leaving only ~1.06% consistent sequence divergence between humans and chimps at shared genes.[89] This nucleotide by nucleotide difference is dwarfed, however, by the portion of each genome that is not shared, including around 6% of functional genes that are unique to either humans or chimps.[90]

In other words, the considerable observable differences between humans and chimps may be due as much or more to genome level variation in the number, function and expression of genes rather than DNA sequence changes in shared genes. Indeed, even within humans, there has been found to be a previously unappreciated amount of copy number variation (CNV) which can make up as much as 5 15% of the human genome. In other words, between humans, there could be +/- 500,000,000 base pairs of DNA, some being active genes, others inactivated, or active at different levels. The full significance of this finding remains to be seen. On average, a typical human protein-coding gene differs from its chimpanzee ortholog by only two amino acid substitutions; nearly one third of human genes have exactly the same protein translation as their chimpanzee orthologs. A major difference between the two genomes is human chromosome 2, which is equivalent to a fusion product of chimpanzee chromosomes 12 and 13.[91] (later renamed to chromosomes 2A and 2B, respectively).

Humans have undergone an extraordinary loss of olfactory receptor genes during our recent evolution, which explains our relatively crude sense of smell compared to most other mammals. Evolutionary evidence suggests that the emergence of color vision in humans and several other primate species has diminished the need for the sense of smell.[92]

In September 2016, scientists reported that, based on human DNA genetic studies, all non-Africans in the world today can be traced to a single population that exited Africa between 50,000 and 80,000 years ago.[93]

The human mitochondrial DNA is of tremendous interest to geneticists, since it undoubtedly plays a role in mitochondrial disease. It also sheds light on human evolution; for example, analysis of variation in the human mitochondrial genome has led to the postulation of a recent common ancestor for all humans on the maternal line of descent (see Mitochondrial Eve).

Due to the lack of a system for checking for copying errors, mitochondrial DNA (mtDNA) has a more rapid rate of variation than nuclear DNA. This 20-fold higher mutation rate allows mtDNA to be used for more accurate tracing of maternal ancestry. Studies of mtDNA in populations have allowed ancient migration paths to be traced, such as the migration of Native Americans from Siberia or Polynesians from southeastern Asia. It has also been used to show that there is no trace of Neanderthal DNA in the European gene mixture inherited through purely maternal lineage.[94] Due to the restrictive all or none manner of mtDNA inheritance, this result (no trace of Neanderthal mtDNA) would be likely unless there were a large percentage of Neanderthal ancestry, or there was strong positive selection for that mtDNA (for example, going back 5 generations, only 1 of your 32 ancestors contributed to your mtDNA, so if one of these 32 was pure Neanderthal you would expect that ~3% of your autosomal DNA would be of Neanderthal origin, yet you would have a ~97% chance to have no trace of Neanderthal mtDNA).

Epigenetics describes a variety of features of the human genome that transcend its primary DNA sequence, such as chromatin packaging, histone modifications and DNA methylation, and which are important in regulating gene expression, genome replication and other cellular processes. Epigenetic markers strengthen and weaken transcription of certain genes but do not affect the actual sequence of DNA nucleotides. DNA methylation is a major form of epigenetic control over gene expression and one of the most highly studied topics in epigenetics. During development, the human DNA methylation profile experiences dramatic changes. In early germ line cells, the genome has very low methylation levels. These low levels generally describe active genes. As development progresses, parental imprinting tags lead to increased methylation activity.[95][96]

Epigenetic patterns can be identified between tissues within an individual as well as between individuals themselves. Identical genes that have differences only in their epigenetic state are called epialleles. Epialleles can be placed into three categories: those directly determined by an individuals genotype, those influenced by genotype, and those entirely independent of genotype. The epigenome is also influenced significantly by environmental factors. Diet, toxins, and hormones impact the epigenetic state. Studies in dietary manipulation have demonstrated that methyl-deficient diets are associated with hypomethylation of the epigenome. Such studies establish epigenetics as an important interface between the environment and the genome.[97]

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