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Mapping a new spontaneous preterm birth susceptibility gene,IGF1R,using linkage,haplotype sharing,and association analysis
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نویسنده
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haataja r. ,karjalainen m.k. ,luukkonen a. ,teramo k. ,puttonen h. ,ojaniemi m. ,varilo t. ,chaudhari b.p. ,plunkett j. ,murray j.c. ,mccarroll s.a. ,peltonen l. ,muglia l.j. ,palotie a. ,hallman m.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 2
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چکیده
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Preterm birth is the major cause of neonatal death and serious morbidity. most preterm births are due to spontaneous onset of labor without a known cause or effective prevention. both maternal and fetal genomes influence the predisposition to spontaneous preterm birth (sptb),but the susceptibility loci remain to be defined. we utilized a combination of unique population structures,family-based linkage analysis,and subsequent case-control association to identify a susceptibility haplotype for sptb. clinically well-characterized sptb families from northern finland,a subisolate founded by a relatively small founder population that has subsequently experienced a number of bottlenecks,were selected for the initial discovery sample. genome-wide linkage analysis using a high-density single-nucleotide polymorphism (snp) array in seven large northern finnish non-consanginous families identified a locus on 15q26.3 (hlod 4.68). this region contains the igf1r gene,which encodes the type 1 insulin-like growth factor receptor igf-1r. haplotype segregation analysis revealed that a 55 kb 12-snp core segment within the igf1r gene was shared identical-by-state (ibs) in five families. a follow-up case-control study in an independent sample representing the more general finnish population showed an association of a 6-snp igf1r haplotype with sptb in the fetuses,providing further evidence for igf1r as a sptb predisposition gene (frequency in cases versus controls 0.11 versus 0.05,p = 0.001,odds ratio 2.3). this study demonstrates the identification of a predisposing,low-frequency haplotype in a multifactorial trait using a well-characterized population and a combination of family and case-control designs. our findings support the identification of the novel susceptibility gene igf1r for predisposition by the fetal genome to being born preterm. © 2011 haataja et al.
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آدرس
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department of pediatrics,institute of clinical medicine,university of oulu,oulu, Finland, department of pediatrics,institute of clinical medicine,university of oulu,oulu, Finland, department of pediatrics,institute of clinical medicine,university of oulu,oulu, Finland, department of obstetrics and gynecology,university central hospital,helsinki, Finland, department of obstetrics and gynecology,university central hospital,helsinki, Finland, department of pediatrics,institute of clinical medicine,university of oulu,oulu, Finland, department of medical genetics,haartman institute,university of helsinki and helsinki university central hospital,helsinki,finland,national institute for health and welfare (thl),helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki, Finland, department of pediatrics,washington university school of medicine,st. louis,mo, United States, department of pediatrics,vanderbilt university school of medicine,nashville,tn,united states,human and statistics genetics program,washington university school of medicine,st. louis,mo, United States, department of pediatrics,university of iowa,iowa city,ia, United States, department of genetics,harvard medical school,boston,ma, United States, department of medical genetics,haartman institute,university of helsinki and helsinki university central hospital,helsinki,finland,national institute for health and welfare (thl),helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,the broad institute of massachusetts institute of technology,harvard university,cambridge,ma,united states,wellcome trust sanger institute,cambridge, United Kingdom, department of pediatrics,vanderbilt university school of medicine,nashville,tn, United States, department of medical genetics,haartman institute,university of helsinki and helsinki university central hospital,helsinki,finland,institute for molecular medicine finland (fimm),university of helsinki,helsinki,finland,the broad institute of massachusetts institute of technology,harvard university,cambridge,ma,united states,wellcome trust sanger institute,cambridge, United Kingdom, department of pediatrics,institute of clinical medicine,university of oulu,oulu, Finland
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Authors
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