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A three‐allelic polymorphic system in exon 12 of the LDL receptor gene is highly informative for segregation analysis of familial hypercholesterolemia in the Spanish population
Author(s) -
Puig Oscar,
Chaves F. Javier,
GarcíaSogo Magdalena,
Real José,
Gil José V.,
Armengod M. Eugenia
Publication year - 1996
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1996.tb02346.x
Subject(s) - genetics , allele , biology , exon , single strand conformation polymorphism , polymorphism (computer science) , population , restriction fragment length polymorphism , familial hypercholesterolemia , microbiology and biotechnology , gene , genotype , medicine , cholesterol , endocrinology , environmental health
We have screened exon 12 of the low density lipoprotein (LDL) receptor gene from 46 familial hypercholesterolemia (FH) heterozygotes and 64 normolipidemic controls for two polymorphisms, Hindi , which is caused by a T to C substitution at base 1773, and a C to T transition at base 1725, by using single strand conformation polymorphism (SSCP) analysis. Our results indicate that polymorphism at base 1725, previously reported as very rare from a Japanese sample, is quite frequent in the Spanish population and that it is closely linked to the presence of the Hindi site ( Hinc II + ). Thus, both polymorphisms constitute a system of three alleles, typed Hinc II ‐ C 1725 , Hinc II + C 1725 , and Hinc II + T 1725 , whose frequencies in the FH sample were 0.489,0.347, and 0.164, respectively. No significant differences were found in the allele frequencies between the FH and control samples. This three‐allelic polymorphic system provides a higher information content (PIC value) than the Hindi RFLP alone (0.537 versus 0.373, respectively); therefore, it is an extremely useful marker for linkage analysis of FH in Caucasian populations.