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exposing the human genome’s evolutionary weaknesses

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exposing the human genome’s evolutionary weaknesses

Both good and bad mutations exist. They can assist an organism in surviving and adapting. Sometimes they are so harmful to an organism that it is impossible for it to live or reproduce. A computer program developed by Professor Adam Siepel's group at Cold Spring Harbor Laboratory (CSHL) tracks the evolution of harmful mutations in the human genome. They discovered that certain regions of the genome are particularly susceptible to mutation, which means that any mutations in those areas could have fatal or severe consequences. Clinicians looking for the origins of serious genetic diseases may benefit from their findings. ExtRaINSIGHT is the name of Siepel's program. By looking for their absence, it looks for harmful mutations. Every part of the human genome should have mutations, but some do not, by chance. These locations are called "ultraselected" by Siepel. Mutations there can be fatal or significantly reduce the likelihood of reproduction when they occur. Siepel elaborates: "If we look at a panel of a hundred thousand humans and never see a mutation at a particular gene, it suggests that any mutation that did occur was so harmful that those who carried it died out of the population," the researchers wrote. Using ExtRaINSIGHT, the team looked at over 70,000 human genomes. Three parts of the genome have been extremely susceptible to mutations over generations, they discovered. Splice sites are the most sensitive of these. Splice sites aid in the development of accurate protein-making instructions. The likelihood of passing on genes, or fitness, can be significantly affected by these mutations. They are associated with a number of diseases, the most common genetic cause of infant and toddler death being spinal muscular atrophy. Siepel writes: "You should take a mutation in a splice site very seriously. Your fitness would be reduced by just that mutation by 1 or 2%. Although that may not sound like much, it has a significant impact on fitness. And if you had more than one of these, your chances of passing on your genes might soon be almost nonexistent." Genes in the central nervous system and molecules called miRNA are also sensitive. According to Siepel, "if you find a mutation in miRNA, there is a good chance that it is the cause of a genetic disease." Additionally, the nervous system appears to be particularly susceptible to mutation due to its complexity and interconnectedness." Many genetic diseases and conditions have no known cause. Siepel believes that technology like ExtRaINSIGHT will assist in identifying their origins and directing future treatments and diagnoses. He also hopes that his work will show how mutations continue to shape the human genome's evolution.

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