title: Genomewide significant linkage to stuttering on chromosome 12.
abstract: Stuttering is a common and sometimes severe communication disorder, of unknown primary etiology, that exists in populations worldwide. Many types of evidence suggest a genetic contribution to stuttering; however, the complex inheritance of this disorder has hindered identification of these factors. We have employed highly inbred families to increase the power of linkage analysis of this disorder. Forty-four Pakistani families with documented or probable consanguinity, from the city of Lahore and surrounding areas, were included. Each family contained multiple cases of stuttering, which were diagnosed using the Stuttering Severity Instrument. Using the Marshfield Weber 9 marker panel, we performed a genomewide linkage scan focused on affected individuals and their parents. The analysis included 199 genotyped individuals, 144 affected and 55 unaffected. The Pedigree Relationship Statistical Test (PREST) was used to identify pedigrees that required additional specification of inbreeding. Initial nonparametric analysis gave evidence of linkage on chromosomes 1, 5, 7, and 12. Additional genotyping was performed on chromosome 12 to a 5-cM level of resolution, and 16 additional individuals were then included, bringing the number of families to 46. Analysis of the enlarged data set provided consistent evidence of linkage on chromosome 12: the S(homoz) scoring function gave a nonparametric LOD score of 4.61, and a LOD score of 3.51 was obtained using the S(all) scoring function. These results suggest that a locus on chromosome 12q may contain a gene with a large effect in this sample.
authors.affiliation: National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, USA.
authors.forename: Naveeda
authors.initials: N
authors.lastname: Riaz
authors.forename: Stacy
authors.initials: S
authors.lastname: Steinberg
authors.forename: Jamil
authors.initials: J
authors.lastname: Ahmad
authors.forename: Anna
authors.initials: A
authors.lastname: Pluzhnikov
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Dennis
authors.initials: D
authors.lastname: Drayna
mesh_terms: D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D003241:Consanguinity; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D013342:Stuttering / Q000235:genetics*
references.citation: Biometrics. 1994 Mar;50(1):118-27
references.pmid: 8086596
references.citation: J Speech Hear Res. 1996 Aug;39(4):771-84
references.pmid: 8844557
references.citation: J Speech Lang Hear Res. 1997 Aug;40(4):778-91
references.pmid: 9263943
references.citation: Am J Hum Genet. 1997 Nov;61(5):1179-88
references.pmid: 9345087
references.citation: Am J Hum Genet. 1998 Jul;63(1):259-66
references.pmid: 9634505
references.citation: Am J Hum Genet. 1999 Nov;65(5):1473-5
references.pmid: 10521318
references.citation: Am J Hum Genet. 1991 Jan;48(1):22-5
references.pmid: 1985459
references.citation: Nat Genet. 2000 May;25(1):12-3
references.pmid: 10802644
references.citation: Nat Genet. 2002 Jan;30(1):97-101
references.pmid: 11731797
references.citation: Genet Epidemiol. 2001;21 Suppl 1:S36-41
references.pmid: 11793699
references.citation: Am J Med Genet A. 2004 Jan 15;124A(2):133-5
references.pmid: 14699610
references.citation: J Speech Hear Res. 1981 Sep;24(3):317-21
references.pmid: 7197739
references.citation: Am J Hum Genet. 2000 Mar;66(3):1076-94
references.pmid: 10712219