Human Genetics

Variants may affect disease heritability

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Science  15 Jun 2018:
Vol. 360, Issue 6394, pp. 1199-1200
DOI: 10.1126/science.360.6394.1199-e

Huntington's disease (HD) is a late-onset neurodegenerative disease caused by the inheritance of an expansion of a trinucleotide repeat in the huntingtin (HTT) gene. A Venezuelan population exhibits an earlier onset of HD than is observed in individuals of European ancestry. Chao et al. sequenced alleles from ∼400 Venezuelan individuals carrying a pathogenic HTT allele. Although Venezuelan sequence–specific changes were evident in the allele, they did not explain early onset of HD. A genome-wide investigation comparing European and Venezuelan individuals revealed other Mendelian modifying genes. This study demonstrates the importance of population-specific investigations of genetic diseases.

PLOS Genet. 10.1371/journal.pgen.1007274 (2018).

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