Scientists map 25 genes that kill fetuses, revealing hidden costs of genetic variants
Researchers analyzed 1.52 million people to identify genes whose mutations are so deadly in the womb that they almost never appear in living populations. The findings could reshape genetic screening programs, drug development priorities, and how insurers and regulators assess genetic risk in prenatal testing and population health initiatives.
Originaltitel: Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
<p>Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.</p>