Document Detail


Whole genomewide linkage screen for neural tube defects reveals regions of interest on chromosomes 7 and 10.
MedLine Citation:
PMID:  15831595     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neural tube defects (NTDs) are the second most common birth defects (1 in 1000 live births) in the world. Periconceptional maternal folate supplementation reduces NTD risk by 50-70%; however, studies of folate related and other developmental genes in humans have failed to definitively identify a major causal gene for NTD. The aetiology of NTDs remains unknown and both genetic and environmental factors are implicated. We present findings from a microsatellite based screen of 44 multiplex pedigrees ascertained through the NTD Collaborative Group. For the linkage analysis, we defined our phenotype narrowly by considering individuals with a lumbosacral level myelomeningocele as affected, then we expanded the phenotype to include all types of NTDs. Two point parametric analyses were performed using VITESSE and HOMOG. Multipoint parametric and nonparametric analyses were performed using ALLEGRO. Initial results identified chromosomes 7 and 10, both with maximum parametric multipoint lod scores (Mlod) >2.0. Chromosome 7 produced the highest score in the 24 cM interval between D7S3056 and D7S3051 (parametric Mlod 2.45; nonparametric Mlod 1.89). Further investigation demonstrated that results on chromosome 7 were being primarily driven by a single large pedigree (parametric Mlod 2.40). When this family was removed from analysis, chromosome 10 was the most interesting region, with a peak Mlod of 2.25 at D10S1731. Based on mouse human synteny, two candidate genes (Meox2, Twist1) were identified on chromosome 7. A review of public databases revealed three biologically plausible candidates (FGFR2, GFRA1, Pax2) on chromosome 10. The results from this screen provide valuable positional data for prioritisation of candidate gene assessment in future studies of NTDs.
Authors:
E Rampersaud; A G Bassuk; D S Enterline; T M George; D G Siegel; E C Melvin; J Aben; J Allen; A Aylsworth; T Brei; J Bodurtha; C Buran; L E Floyd; P Hammock; B Iskandar; J Ito; J A Kessler; N Lasarsky; P Mack; J Mackey; D McLone; E Meeropol; L Mehltretter; L E Mitchell; W J Oakes; J S Nye; C Powell; K Sawin; R Stevenson; M Walker; S G West; G Worley; J R Gilbert; M C Speer
Related Documents :
11393795 - Genome screen for quantitative trait loci underlying normal variation in femoral struct...
19461885 - Admixture mapping of 15,280 african americans identifies obesity susceptibility loci on...
11986135 - A genome-wide scan for linkage to chromosomal regions in 382 sibling pairs with schizop...
8579335 - An extension of the maximum lod score method to x-linked loci.
16501995 - Cotton genome mapping with new microsatellites from acala 'maxxa' bac-ends.
1740325 - A possible mosaic form of delayed centromere separation and aneuploidy.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2005-04-14
Journal Detail:
Title:  Journal of medical genetics     Volume:  42     ISSN:  1468-6244     ISO Abbreviation:  J. Med. Genet.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-05     Completed Date:  2006-07-17     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2985087R     Medline TA:  J Med Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  940-6     Citation Subset:  IM    
Affiliation:
Duke University Medical Center, Box 3445, Durham, NC 27710, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Chromosomes, Human, Pair 10*
Chromosomes, Human, Pair 7*
Family Health
Female
Genetic Markers
Genome, Human*
Genotype
Humans
Linkage (Genetics)*
Male
Models, Genetic
Neural Crest / pathology*
Neural Tube Defects / genetics*
Pedigree
Physical Chromosome Mapping
Grant Support
ID/Acronym/Agency:
ES011961/ES/NIEHS NIH HHS; ES11375/ES/NIEHS NIH HHS; HD39081/HD/NICHD NIH HHS; HD39083/HD/NICHD NIH HHS; HD39195/HD/NICHD NIH HHS; HD39948/HD/NICHD NIH HHS; NS046249/NS/NINDS NIH HHS; NS26630/NS/NINDS NIH HHS; NS39818/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Genetic Markers
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Methodological issues in longitudinal studies: vestibular schwannoma growth rates in neurofibromatos...
Next Document:  Primary percutaneous coronary intervention versus thrombolytic treatment: long term follow up accord...