Reconstruction of ancestral haplotypes in a 12-generation schizophrenia pedigree

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Lindholm, EvaUppsala universitet,Evolutionsbiologi (author)

Reconstruction of ancestral haplotypes in a 12-generation schizophrenia pedigree

Article/chapterEnglish2004

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Philadelphia :Lippincott Williams & Wilkins,2004
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LIBRIS-ID:oai:DiVA.org:umu-122177
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-122177URI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-93324URI

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Language:English
Summary in:English

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We searched for candidate chromosomal regions inherited identical by descent in 19 patients suffering from schizophrenia or schizoaffective disorder that are related 12 generations back, to an ancestral couple born in the middle of the seventeenth century. To accomplish this goal, we constructed complete chromosomal haplotypes for each patient using genotype data from 450 markers. In total, 12 haplotype regions (with sizes ranging from 0.6 to 10.9 cM) constituted by three markers each were identical in three or more of the affected individuals. The largest genomic segment was located on 6q25, a region previously shown to be significantly more frequent in patients than controls, and proposed to contain a schizophrenia susceptibility locus. For the remaining 11 candidate haplotypes, we estimated haplotype frequencies from all the 43 affected members collected from the same family and 46 unrelated control individuals. This analysis indicated that at least four of the 11 candidate haplotypes are ancestral, since the frequencies were significantly higher in patients than in controls. Five additional haplotypes showed higher estimated frequencies in the patients but the differences were not significant. Interestingly, five of these 11 genomic regions are located in, or close to, candidate regions previously suggested to contain susceptibility genes for schizophrenia. The regions are 5q21-23, 8p21-22, 1 0p13-15, 13q12-13 and 22q12-13. Several of these haplotypes are probably ancestral linkage disequilibrium blocks inherited from the original couple. There exists, however, the possibility that one or more of these regions harbour schizophrenia susceptibility loci that may have epistatic interactions among them.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
NATURVETENSKAP Biologi Genetik hsv//swe
NATURAL SCIENCES Biological Sciences Genetics hsv//eng
psychiatric genetics
schizophrenia
ancestral haplotypes
susceptibility loci
Genetics

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Åberg, KarolinaUppsala universitet,Evolutionsbiologi (author)
Ekholm, BirgitUmeå universitet,Psykiatri (author)
Pettersson, UlfUppsala universitet,Evolutionsbiologi (author)
Adolfsson, RolfUmeå universitet,Psykiatri(Swepub:umu)road0001 (author)
Jazin, ElenaUppsala universitet,Evolutionsbiologi(Swepub:uu)elenjazi (author)
Uppsala universitetEvolutionsbiologi (creator_code:org_t)

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In:Psychiatric GeneticsPhiladelphia : Lippincott Williams & Wilkins14:1, s. 1-80955-88291473-5873

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By the author/editor: Lindholm, Eva; Åberg, Karolina; Ekholm, Birgit; Pettersson, Ulf; Adolfsson, Rolf; Jazin, Elena

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Genetics

Articles in the publication: Psychiatric Gene ...

By the university: Umeå University; Uppsala University

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