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Pregled bibliografske jedinice broj: 771674

Homozygous loss-of-function variants in European cosmopolitan and isolate populations

Kaiser, V.B.; ...; Patarčić, Inga; ...; Miljković, Ana; ...; Rudan, Igor; ...; Polašek, Ozren; ... : Wilson, James
Homozygous loss-of-function variants in European cosmopolitan and isolate populations // Human molecular genetics, 24 (2015), 19; 5464-5474 doi:10.1093/hmg/ddv272 (međunarodna recenzija, članak, znanstveni)

Homozygous loss-of-function variants in European cosmopolitan and isolate populations

Kaiser, V.B. ; ... ; Patarčić, Inga ; ... ; Miljković, Ana ; ... ; Rudan, Igor ; ... ; Polašek, Ozren ; ... : Wilson, James

Human molecular genetics (0964-6906) 24 (2015), 19; 5464-5474

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Knock-out; homozygous

Homozygous loss of function (HLOF) variants provide a valuable window on gene function in humans, as well as an inventory of the human genes that are not essential for survival and reproduction. All humans carry at least a few HLOF variants, but the exact number of inactivated genes that can be tolerated is currently unknown-as are the phenotypic effects of losing function for most human genes. Here, we make use of 1432 whole exome sequences from five European populations to expand the catalogue of known human HLOF mutations ; after stringent filtering of variants in our dataset, we identify a total of 173 HLOF mutations, 76 (44%) of which have not been observed previously. We find that population isolates are particularly well suited to surveys of novel HLOF genes because individuals in such populations carry extensive runs of homozygosity, which we show are enriched for novel, rare HLOF variants. Further, we make use of extensive phenotypic data to show that most HLOFs, ascertained in population-based samples, appear to have little detectable effect on the phenotype. On the contrary, we document several genes directly implicated in disease that seem to tolerate HLOF variants. Overall HLOF genes are enriched for olfactory receptor function and are expressed in testes more often than expected, consistent with reduced purifying selection and incipient pseudogenisation

Izvorni jezik

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Javno zdravstvo i zdravstvena zaštita


Projekt / tema
216-1080315-0302 - Odrednice zdravlja i bolesti u općoj i izoliranim ljudskim populacijama (Ozren Polašek, )
HRZZ-IP-2013-11-8875 - Pleitropija, genske mreže i putevi u izoliranim ljudskim populacijama: 10.001 Dalmatinac (Ozren Polašek, )

Medicinski fakultet, Split

Časopis indeksira:

  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus