Measures of autozygosity in decline: globalization, urbanization, and its implications for medical genetics

• Published in: PLoS genetics 2009-03, Vol.5 (3), p.e1000415-e1000415
• Main Authors: Nalls, Michael A, Simon-Sanchez, Javier, Gibbs, J Raphael, Paisan-Ruiz, Coro, Bras, Jose Tomas, Tanaka, Toshiko, Matarin, Mar, Scholz, Sonja, Weitz, Charles, Harris, Tamara B, Ferrucci, Luigi, Hardy, John, Singleton, Andrew B
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aging; Causes of; Consanguinity; Demographic aspects; Genetic disorders; Genetic variation; Genetics; Genetics and Genomics; Genetics and Genomics/Bioinformatics; Genetics and Genomics/Medical Genetics; Genetics and Genomics/Population Genetics; Genetics, Medical; Genetics, Population; Genome, Human; Homozygote; Human genetics; Humans; Inbreeding; Medical research; Middle Aged; Models, Statistical; North America; Statistical models; Urbanization; Young Adult
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000415

This research investigates the influence of demographic factors on human genetic sub-structure. In our discovery cohort, we show significant demographic trends for decreasing autozygosity associated with population variation in chronological age. Autozygosity, the genomic signature of consanguinity, is identifiable on a genome-wide level as extended tracts of homozygosity. We identified an average of 28.6 tracts of extended homozygosity greater than 1 Mb in length in a representative population of 809 unrelated North Americans of European descent ranging in chronological age from 19-99 years old. These homozygous tracts made up a population average of 42 Mb of the genome corresponding to 1.6% of the entire genome, with each homozygous tract an average of 1.5 Mb in length. Runs of homozygosity are steadily decreasing in size and frequency as time progresses (linear regression, p