Idioma:

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

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 Visscher, Peter M.

PLoS genetics, 2009-03, Vol.5 (3), p.e1000415-e1000415 [Periódico revisado por pares]

United States: Public Library of Science

Texto completo disponível

Citações Citado por

Enviar para

Título:
Measures of autozygosity in decline: globalization, urbanization, and its implications for medical genetics
Autor: 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
Visscher, Peter M.
Assuntos: 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
É parte de: PLoS genetics, 2009-03, Vol.5 (3), p.e1000415-e1000415
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
These authors are joint first authors of this work.
Conceived and designed the experiments: JH ABS. Performed the experiments: JSS CPR SS. Analyzed the data: MAN JSS JRG TT CW LF ABS. Contributed reagents/materials/analysis tools: JSS JTB TT MM CW TBH LF JH ABS. Wrote the paper: MAN JSS ABS.
Descrição: 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<0.05). We also calculated inbreeding coefficients and showed a significant trend for population-wide increasing heterozygosity outside of linkage disequilibrium. We successfully replicated these associations in a demographically similar cohort comprised of a subgroup of 477 Baltimore Longitudinal Study of Aging participants. We also constructed statistical models showing predicted declining rates of autozygosity spanning the 20th century. These predictive models suggest a 14.0% decrease in the frequency of these runs of homozygosity and a 24.3% decrease in the percent of the genome in runs of homozygosity, as well as a 30.5% decrease in excess homozygosity based on the linkage pruned inbreeding coefficients. The trend for decreasing autozygosity due to panmixia and larger effective population sizes will likely affect the frequency of rare recessive genetic diseases in the future. Autozygosity has declined, and it seems it will continue doing so.
Editor: United States: Public Library of Science
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

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

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 Visscher, Peter M.

United States: Public Library of Science

Buscando em bases de dados remotas. Favor aguardar.