Mapping of a gene for X-linked agammaglobulinemia and evidence for genetic heterogeneity.
X-linked agammaglobulinemia (XLA) is a severe humoral immunodeficiency disease of man. The inheritance of the disease is X-linked recessive. Female carriers can not be distinguished by immunologic assays. We investigated the localization of the disease gene on the X chromosome, utilizing nine polymorphic X chromosomal markers. In a single eight generation pedigree we found close linkage of the disease gene to the restriction fragment length polymorphism (RFLP) recognized by the DNA probe p19-2; the maximum lod score was 3.30 at a recombination fraction of 0.06. Addition of the lod scores for p19-2 obtained from seven other XLA pedigrees did not show the expected increase of the total score. This suggested genetic heterogeneity. We used the p19-2 marker as a reference point to search for pedigrees which had the disease gene at a different location. One pedigree provided a lod score of -3.14 at a recombination fraction of 0.06 with the p19-2 marker. We postulate that XLA is not a single genetic entity.
D000361:Agammaglobulinemia / Q000235:genetics*; D000483:Alleles; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D014960:X Chromosome
D005819:Genetic Markers