Two microsatellite polymorphisms at the D5S39 locus.
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Base Sequence↗
Biomedical subjects
G Kalsi
Publications and source records attributed to G Kalsi.
A TaqI polymorphism detected by a genomic clone at the locus D5S39 (5q11-13).
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Alleles↗
A cosmid clone for the 5HT1A receptor (HTR1A) reveals a TaqI RFLP that shows tight linkage to dna loci D5S6, D5S39, and D5S76.
A human neuroreceptor clone (G21), which was isolated by cross-hybridization with the human clone for the beta 2-adrenergic receptor, has recently been shown to encode the gene for the 5HT1A receptor (HTR1A) subtype. In situ hybridization to human metaphase chromosomes mapped the G21 sequence to chromosome 5 at bands 5q11.2-q13. The clone G21 recognizes a SacI RFLP with low heterozygosity (0.13). To increase the informativeness of the HTR1A locus we have isolated two new cosmid clones containing the receptor gene. No polymorphic microsatellites were present in the cosmids. However, one cosmid revealed a new TaqI RFLP that showed tight linkage to new highly polymorphic microsatellites for the loci D5S76, D5S39, and D5S6 in seven British and Icelandic reference pedigrees (maximum LOD of 13.2 with D5S76).
Chromosome Mapping↗
Linkage disequilibrium between two highly polymorphic microsatellites.
The PCR was used to amplify genomic DNA from two microsatellite (dC-dA)n.(dG-dT)n sequences found to be present in the same chromosome 5 genomic clone. Analysis of the haplotype frequencies of these two interspersed repeat sequences in individuals showed strong allelic association or linkage disequilibrium. Six alleles were found for p599 (CA)n with a PIC value of 0.71 and 8 alleles were seen for lambda 599 (CA)n with a PIC value of 0.74. The two microsatellites are separated by approximately 7 kb. Analysis of the length variations for the two microsatellites showed that they were positively correlated, a finding that has no obvious explanation. The strong linkage disequilibrium found demonstrates stability during evolution for these novel markers. Therefore they should be powerful new tools for studying genetic drift and admixture of populations. Furthermore, disequilibrium data from microsatellites can be used in the fine mapping and cloning of disease genes.
Alleles↗
Microsatellite polymorphisms for chromosome 5 bands q11.2-q13.3.
The genes for spinal muscular atrophy (SMA) and a possible subtype of schizophrenia (SCZD1) have been mapped to chromosome 5q11.2-q13.3. DNA markers have been mapped to 5q11.2-q13.3 using a hybrid cell line deleted for this region [Gilliam et al., Genomics 1989;5:940-944]. Genomic lambda clones for these markers facilitated the identification of highly polymorphic microsatellites. A total of ten microsatellites were identified and sequenced. Of these, seven were found to be polymorphic. Four had polymorphism information content values > 0.7. New polymorphic microsatellites were sequenced for D5S76, D5S125, D5S39, D5S127 and HEX-B. Two-point and multipoint analysis in non-CEPH pedigrees confirmed that the microsatellites were in tight linkage with each other. These new microsatellites will increase the efficiency of linkage analysis for these disorders.
Alleles↗
Linkage analysis of manic depression (bipolar affective disorder) in Icelandic and British kindreds using markers on the short arm of chromosome 18.
Attempts were made to follow up results of a previous linkage study which suggested that a locus-modifying susceptibility to bipolar and related unipolar affective disorder might be present in the pericentromeric region of the short arm of chromosome 18. Twenty-three multiply affected pedigrees collected from Iceland and the UK were genotyped using three highly polymorphic microsatellite markers at D18S37, D18S40 and D18S44 which span the region implicated. Lod score analyses under the assumption of heterogeneity and non-parametric linkage analyses were performed. The total lod scores obtained were strongly negative, and analysis allowing for heterogeneity did not suggest that any subgroup of the families was linked. Model-free linkage analysis using extended relative pair analysis and MFLINK also failed to detect any evidence for linkage. Our study provides no support for the presence of a locus-modifying genetic susceptibility to bipolar affective disorder in the pericentromeric region of chromosome 18q11. Further analyses in independent samples should help to reveal whether our negative results are due to locus heterogeneity or whether the original results were false-positive.
Alleles↗