Characterization of the highly discriminatory loci DYS449, DYS481, DYS518, DYS612, DYS626, DYS644 and DYS710.

During the study of genetic diversity at non-core Y-STRs in South African population groups, we identified loci with high discrimination capacity. In this study we present a detailed account of the allele diversity, allele sequence data, gene diversity, allele frequency spectrum and informativeness for assignment in the European English, Asian Indian and Xhosa population groups at loci DYS449, DYS481, DYS518, DYS612, DYS626, DYS644 and DYS710. The suitability of these loci for forensic, genealogical and evolutionary studies is discussed, and nomenclature for loci DYS518, DYS612, DYS626 and DYS644 is suggested.

Analysis of seventeen Y-chromosome STR loci in the Cape Muslim population of South Africa.

Two Y-STR genotyping systems were evaluated for usefulness in forensic casework in the Cape Muslim population of South Africa. Samples were collected from 105 males, and genotyped for 17 loci amplified in two multiplexes. Allele and haplotype frequencies were determined for nine Y-STR loci used to define the minimal haplotype (DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393, and the duplicated locus DYS385) amplified in one multiplex, as well as for eight widely used loci amplified in a second multiplex and consisting of DYS449, DYS481, DYS518, DYS557, DYS570, DYS607, DYS612 and DYS614. When analysing the samples for all the loci, 104 unique haplotypes were obtained, and the discrimination capacity was 0.990. When considering only the nine Y-STRs included in the minimal haplotype, 91 unique haplotypes were obtained, and the discrimination capacity was 0.866. In the case of the remaining eight Y-STR loci, values of 97 and 0.924 were obtained, respectively.

Nine-locus Y-STR profiles of Afrikaner Caucasian and mixed ancestry populations from Cape Town, South Africa.

Samples were collected from 108 Afrikaner males and 114 males of mixed ancestry. The term mixed ancestry is being used to denote a complex community which was established with contributions from Asians, Caucasians and Indigenous populations and constitutes a significant proportion of the Cape Town metropolitan population. Allele and haplotype frequencies were determined for nine Y-STR loci (DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393 and the duplicated locus DYS385). Unique haplotypes were obtained for 64 Afrikaner males and 90 males of mixed ancestry. Both population groups shared the same most common haplotype.

Properties of novel and widely studied Y-STR loci in three South African populations.

The objective of the present study was to examine the properties of a set of single-copy Y-STR loci to assess their suitability for forensic casework in three South African populations. Three criteria were used to select markers for assessment. Firstly, the single-copy markers of the minimal haplotype were selected based on their established use in forensic studies. Secondly, 8 markers were selected on the basis of high gene diversity values reported for several population studies, and thirdly 19 markers were chosen from a survey of Y-chromosome sequence with selections made primarily on the basis of the number of repeated elements present. Samples were typed from 101 English-speaking Caucasians, 88 Xhosa individuals and 77 Asian Indians. Gene diversity values, the number of alleles identified and the average stutter was determined for each locus.

Apoptosis-inducing signal sequence mutation in carbonic anhydrase IV identified in patients with the RP17 form of retinitis pigmentosa.

Genetic and physical mapping of the RP17 locus on 17q identified a 3.6-megabase candidate region that includes the gene encoding carbonic anhydrase IV (CA4), a glycosylphosphatidylinositol-anchored protein that is highly expressed in the choriocapillaris of the human eye. By sequencing candidate genes in this region, we identified a mutation that causes replacement of an arginine with a tryptophan (R14W) in the signal sequence of the CA4 gene at position -5 relative to the signal sequence cleavage site. This mutation was found to cosegregate with the disease phenotype in two large families and was not found in 36 unaffected family members or 100 controls. Expression of the mutant cDNA in COS-7 cells produced several findings, suggesting a mechanism by which the mutation can explain the autosomal dominant disease. In transfected COS-7 cells, the R14W mutation (i) reduced the steady-state level of carbonic anhydrase IV activity expressed by 28% due to a combination of decreased synthesis and accelerated turnover; (ii) led to up-regulation of immunoglobulin-binding protein, double-stranded RNA-regulated protein kinase-like ER kinase, and CCAAT/enhancer-binding protein homologous protein, markers of the unfolded protein response and endoplasmic reticulum stress; and (iii) induced apoptosis, as evidenced by annexin V binding and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining, in most cells expressing the mutant, but not the WT, protein. We suggest that a high level of expression of the mutant allele in the endothelial cells of the choriocapillaris leads to apoptosis, leading in turn to ischemia in the overlying retina and producing autosomal dominant retinitis pigmentosa.