Replication of linkage of familial hypobetalipoproteinemia to chromosome 3p in six kindreds.
Familial hypobetalipoproteinemia (FHBL) is a genetically heterogeneous condition characterized by very low apolipoprotein B (apoB) concentrations in plasma and/or low levels of LDL-cholesterol (LDL-C) with a propensity to developing fatty liver. In a minority of cases, truncation-specifying mutations of the apoB gene (APOB) are etiologic, but the genetic basis of most cases is unknown. We previously reported linkage of FHBL to a 10 cM region on 3p21.1-22 in one kindred. The objectives of the current study were to identify other FHBL families with linkage to 3p and to narrow the FHBL susceptibility region on 3p. Six additional FHBL kindreds unlinked to the APOB region on chromosome 2 were genotyped with polymorphic markers spanning a region of approximately 13 cM on chromosome 3. Quantitative linkage analyses indicated that the FHBL in these families was linked to 3p21.1-22. Haplotype analysis identified several meiotic crossover events, allowing us to narrow the critical region from 10 cM to 2.0 cM, between markers D3S2407 and D3S1767.
Neuman
Rosalind J
RJ
Washington University School of Medicine, Department of Psychiatry, 660 South Euclid Avenue, Campus Box 8134, St. Louis, MO 63110, USA. roz@gretta.wustl.edu
Yuan
Bo
B
Gerhard
Daniela S
DS
Liu
Kuang-Yu
KY
Yue
Pin
P
Duan
Shenghui
S
Averna
Maurizio
M
Schonfeld
Gustav
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003434:Crossing Over, Genetic / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D019655:Quantitative Trait, Heritable
D005819:Genetic Markers