Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
17186463
TITLE
HLA and genomewide allele sharing in dizygotic twins.
ABSTRACT
Gametic selection during fertilization or the effects of specific genotypes on the viability of embryos may cause a skewed transmission of chromosomes to surviving offspring. A recent analysis of transmission distortion in humans reported significant excess sharing among full siblings. Dizygotic (DZ) twin pairs are a special case of the simultaneous survival of two genotypes, and there have been reports of DZ pairs with excess allele sharing around the HLA locus, a candidate locus for embryo survival. We performed an allele-sharing study of 1,592 DZ twin pairs from two independent Australian cohorts, of which 1,561 pairs were informative for linkage on chromosome 6. We also analyzed allele sharing in 336 DZ twin pairs from The Netherlands. We found no evidence of excess allele sharing, either at the HLA locus or in the rest of the genome. In contrast, we found evidence of a small but significant (P=.003 for the Australian sample) genomewide deficit in the proportion of two alleles shared identical by descent among DZ twin pairs. We reconciled conflicting evidence in the literature for excess genomewide allele sharing by performing a simulation study that shows how undetected genotyping errors can lead to an apparent deficit or excess of allele sharing among sibling pairs, dependent on whether parental genotypes are known. Our results imply that gene-mapping studies based on affected sibling pairs that include DZ pairs will not suffer from false-positive results due to loci involved in embryo survival.
DATE PUBLISHED
2006 Dec
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2006/06/22
accepted 2006/10/05
aheadofprint 2006/10/23
pubmed 2006/12/23 09:00
medline 2007/02/07 09:00
entrez 2006/12/23 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Montgomery GW Montgomery Grant W GW Molecular and Genetic Epidemiology Laboratories, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia. grant.montgomery@qimr.edu.au
Zhu G Zhu Gu G
Hottenga JJ Hottenga Jouke Jan JJ
Duffy DL Duffy David L DL
Heath AC Heath Andrew C AC
Boomsma DI Boomsma Dorret I DI
Martin NG Martin Nicholas G NG
Visscher PM Visscher Peter M PM
INVESTIGATORS
JOURNAL
VOLUME: 79
ISSUE: 6
TITLE: American journal of human genetics
ISOABBREVIATION: Am. J. Hum. Genet.
YEAR: 2006
MONTH: Dec
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
ISSN: 0002-9297
ISSNTYPE: Print
MEDLINE JOURNAL
MEDLINETA: Am J Hum Genet
COUNTRY: United States
ISSNLINKING: 0002-9297
NLMUNIQUEID: 0370475
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA007535 NIAAA NIH HHS United States
AA013320 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
AA07728 NIAAA NIH HHS United States
AA10249 NIAAA NIH HHS United States
AA11998 NIAAA NIH HHS United States
HD042157 NICHD NIH HHS United States
N01-HG-65403 NHGRI NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Alleles
Australia
Female
Genome, Human
Histocompatibility Antigens Class I genetics
Humans genetics
Male genetics
Netherlands genetics
Twins, Dizygotic genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Histocompatibility Antigens Class I
OTHER ID's
OTHERID SOURCE
PMC1698703 NLM