This article is from WeChat official account:Principle (ID: principle1687), the original title of” a milestone on how genes control the height of progress “, author: sugar beast, title figure from: vision China
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In 2008, the journal Nature published a report stating that from the research conducted on identical and fraternal twins over the past century, 80% to 90% of human height is inherited. These studies clearly show that height is largely determined by genes and is a trait with a very high heritability. This means that if there is a difference of 29 cm between the highest 5% of the population and the shortest part of the population, 27 cm of the population may be attributed to genetic factors.
At that time, however, three research groups conducted a genome-wide association study (GWAS, the purpose of which was the largest at the time) involving more than 30,000 people (the largest scale at the time). Searching for common genetic variants related to a certain trait or disease within the genome), the researchers found more than 40 genetic variants related to height differences, but found that these genetic variants have a very Tiny, in general, they only account for a little over 5% of the heritability of height.
So where does the heritability of deletion go? This has puzzled many geneticists, and therefore many speculations have emerged.
Some people think that the GWAS study has missed some rare genetic variants and the interactions between genes; others think that there may be errors in the twin studies in the past. However, some scientists believe that this may be because most of the genes related to the trait of height have not yet been discovered. Over time, more and more related genes may slowly appear.
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Peter Visscher, a geneticist at the University of Queensland, is one of those who uphold the last kind of optimistic view. He believes that the key to this research is to find more genetic mutations that affect the smallest For these weak signals, they need to study the DNA of a large number of people.
In 2010, a research team led by Visscher conducted a genome-wide association study on nearly 3,925 British people, and evaluated a type of single nucleotide polymorphism.(SNP) and personal height. In order to test this correlation, they did not test each SNP separately like some previous similar studies, but used a method called statistical estimation to test nearly 300,000 SNPs for each person at the same time. The results of the study show that the common SNP can explain 45% of the population’s height differences. Given that “80% of height is inherited”, this means that this has reached more than half of the heritability rate.
By 2018, the Visscher team worked with a global alliance called GIANT to aggregate DNA data of 700,000 people, and identified 3290 independent SNPs related to height, and found that these SNPs can explain 25% of the height difference .
Now, an unprecedented large-scale study has brought milestone progress on this subject.
An international team of geneticists including Visscher collected genomic data of more than 4.1 million people of European ancestry through 201 GWAS studies, and identified about 9900 DNA markers that can explain the effect of genetic variation on height. In total, 40% of the height difference can be explained. Researchers believe that other markers located near these markers are likely to explain another 10% of the height difference.
However, even so, this value is still lower than the 80% predicted in the previous twin study.
In 2019, Visscher’s research team used whole-genome sequencing data from a small group of people and found some rare genetic variants (that is, less than 1 in 100 people Human genetic variation) should explain the remaining 30% of height variation. At present, this result has been submitted to theOn the preprint website bioRxiv of Physics, the research team is making further revisions to the results. Perhaps in the near future, we will be able to have a better understanding of the effect of genes on height.
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For this result, some geneticists said it was as they expected-Once the gene sample is large enough, then these missing genetic variants will be filled in. However, some scientists are dissatisfied with the results of this study-they believe that the study identified only the markers related to the genes that affect height, not the genes themselves, and there are very few DNA related to height Markers are associated with specific genes that clearly change height.
Nevertheless, new discoveries offer hope for tracking these genes. These 9900 markers appear in about 30% of the genome, and many of them are clustered in regions known to contain genes related to growth, rather than randomly distributed throughout the genome, which reduces the identification of specific genes and clarification The difficulty of their role.
If the relationship between all the missing genes and other traits and diseases can be confirmed, and extended to people of other bloodlines, then the results of this study may herald new biology and help the development of personalized medicine , And more accurately assess people’s risk of illness.
Reference source:
https://www.sciencemag.org/news/2020/11/landmark-study-resolves-major-mystery-how-genes-govern-human-height
https://www.abstractsonline.com/pp8/#!/9070/presentation/1956
https://pubmed.ncbi.nlm.nih.gov/30124842/#affiliation-1
https://www.nature.com/articles/ng.608
https://www.nature.com/news/2008/081105/full/456018a.html#B2
https://www.biorxiv.org/content/10.1101/588020v1
This article is from WeChat official account:principle (ID: principalia1687), author: sugar beast