title: Localization of a recessive gene for North American Indian childhood cirrhosis to chromosome region 16q22-and identification of a shared haplotype.
abstract: North American Indian childhood cirrhosis (NAIC, or CIRH1A) is an isolated nonsyndromic form of familial cholestasis reported in Ojibway-Cree children and young adults in northwestern Quebec. The pattern of transmission is consistent with an autosomal recessive mode of inheritance. To map the NAIC locus, we performed a genomewide scan on three DNA pools of samples from 13 patients, 16 unaffected siblings, and 22 parents from five families. Analysis of 333 highly polymorphic markers revealed 3 markers with apparent excess allele sharing among affected individuals. Additional mapping identified a chromosome 16q segment shared by all affected individuals. When the program FASTLINK/LINKAGE was used and a completely penetrant autosomal recessive mode of inheritance was assumed, a maximum LOD score of 4.44 was observed for a recombination fraction of 0, with marker D16S3067. A five-marker haplotype (D16S3067, D16S752, D16S2624, D16S3025, and D16S3106) spanning 4.9 cM was shared by all patients. These results provide significant evidence of linkage for a candidate gene on chromosome 16q22.
authors.affiliation: Montreal Genome Centre, Montreal General Hospital Research Institute, Quebec, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Bétard
authors.forename: A
authors.initials: A
authors.lastname: Rasquin-Weber
authors.forename: C
authors.initials: C
authors.lastname: Brewer
authors.forename: E
authors.initials: E
authors.lastname: Drouin
authors.forename: S
authors.initials: S
authors.lastname: Clark
authors.forename: A
authors.initials: A
authors.lastname: Verner
authors.forename: C
authors.initials: C
authors.lastname: Darmond-Zwaig
authors.forename: J
authors.initials: J
authors.lastname: Fortin
authors.forename: J
authors.initials: J
authors.lastname: Mercier
authors.forename: P
authors.initials: P
authors.lastname: Chagnon
authors.forename: T M
authors.initials: TM
authors.lastname: Fujiwara
authors.forename: K
authors.initials: K
authors.lastname: Morgan
authors.forename: A
authors.initials: A
authors.lastname: Richter
authors.forename: T J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: G A
authors.initials: GA
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002779:Cholestasis / Q000235:genetics; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008103:Liver Cirrhosis / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D019683:Penetrance; D011110:Polymorphism, Genetic / Q000235:genetics; D011792:Quebec; D012984:Software
chemical_list: D005819:Genetic Markers