Dinucleotide repeat and alu repeat polymorphisms at the 5-HT1A(HTR1 A) receptor gene

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The human 5-hydroxytryptamine 1A receptor gene (HTRIA) is a candidate gene for neurobehavioral disorders involving serotonergic dysfunction. The gene was isolated and found to be intronless, with a coding region of about 1300 base pairs. The genomic clone G-21 contains the entire coding region and only a few hundred base pairs of flanking sequence. This clone was used to map HTRIA to chromosome 5q11.2–13 by in situ hybridization. A larger HTR1A clone (G21pcos6) was isolated and a two-allele TaqI polymorphism was revealed with this probe. Using this marker, HTRIA was shown to be tightly linked to chromosome 5q markers D5S6, D5S39 and D5S76. Recently, a synonymous variant of HTRIA was detected by DGGE and RFLP analysis. This polymorphic system consists of two alleles, with an observed heterozygosity of 0.34. There is a need to identify additional informative markers at this locus in order to facilitate linkage studies on neurogenetic disorders involving HTRIA. Therefore, using G21 as probe, we isolated genomic clones and scanned the immediate HTRIA region for novel polymorphisms. Partial characterization and sequencing of two of these clones revealed that each had a different DNA repeat sequence exhibiting polymorphism. One clone had a dinucleotide repeat that revealed four alleles. The other had an alu repeat that showed a six-allele polymorphism. Both markers were shown to be informative in a number of CEPH pedigrees.

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