Exclusion of linkage between the human apolipoprotein B gene and abetalipoproteinemia.
Abetalipoproteinemia (ABLP) is a rare autosomal recessive disease characterized by a lack of plasma apolipoprotein B (apo B). In this report, the hypothesis that ABLP is due to rare mutations in the apo B gene was tested. A total of eight ABLP families were studied. Apo B gene RFLPs were used to establish the haplotypes of the apo B alleles in family members. LOD score analysis was used to study the linkage between the apo B alleles and ABLP. These families were categorized arbitrarily as class I, II, III, or IV because of differences in the results derived from both haplotyping and LOD score analysis. In a class I family, affected siblings, who on the basis of the hypothesis would be expected to have the same apo B alleles, had different ones. LOD score analysis of this family gave an infinite negative number at a recombination fraction (theta) of zero. In two class II families, probands who were the result of consanguineous marriages and who, on the basis of the hypothesis, should be homozygotes for a defective apo B allele, were heterozygotes at this locus. The sum of the LOD scores from these two families was -1.7 at theta = 0. In one class III family, a parent was apparently homozygous for a particular apo B allele and yet not affected. This also contributed negatively to the LOD score. In four class IV families, disease inheritance was compatible with segregation of the apo B alleles. This, however, was not statistically significant (LOD score = 0.97 at theta = 0).(ABSTRACT TRUNCATED AT 250 WORDS)
Huang
L S
LS
Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY 10021.
Jänne
P A
PA
de Graaf
J
J
Cooper
M
M
Deckelbaum
R J
RJ
Kayden
H
H
Breslow
J L
JL
Decklebaum
R J
RJ
D000012:Abetalipoproteinemia / Q000235:genetics*; D000483:Alleles; D001055:Apolipoproteins B / Q000235:genetics*; D001483:Base Sequence; D003241:Consanguinity; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D015183:Restriction Mapping
D001055:Apolipoproteins B