Localization of a recessive gene for North American Indian childhood cirrhosis to chromosome region 16q22-and identification of a shared haplotype.
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.
Bétard
C
C
Montreal Genome Centre, Montreal General Hospital Research Institute, Quebec, Canada.
Rasquin-Weber
A
A
Brewer
C
C
Drouin
E
E
Clark
S
S
Verner
A
A
Darmond-Zwaig
C
C
Fortin
J
J
Mercier
J
J
Chagnon
P
P
Fujiwara
T M
TM
Morgan
K
K
Richter
A
A
Hudson
T J
TJ
Mitchell
G A
GA
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
D005819:Genetic Markers