HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in Saudis using next generation sequencing technique.

Next generation sequencing (NGS) is a promising technique that can reveal the entire gene sequences and to the highest possible resolution without any phase ambiguities. We have used this technique to investigate the frequencies of HLA-A, -B, -C, -DRB1 and -DQB1 in a Saudi cohort of healthy individuals. We used NGS using the 454 genome sequence (GS) FLX System and Conexio assign atf 454 software to human leukocyte antigen (HLA) genotype eight class I and class II loci. A total of 158 healthy Saudi adults were analyzed. The most frequently observed allele for HLA-A was HLA-A*02:01:01:01 (13.6%); for HLA-B, HLA-B*50:01:01 (15.8%); for HLA-C, HLA-C*06:02:01:01 (18.7%); for HLA-DRB1, HLA-DRB1*07:01:01:01 (26.6%); and for HLA-DQB1, HLA-DQB1*02:01:01 (20.3%). The most common four loci haplotypes in the Saudi population were HLA-A*24:02:01:01-B*08:01:01-C*07:02:01:01-DRB1*03:01:01:01 and HLA-A*23:01:01-B*50:01:01-C*06:02:01:01-DRB1*07:01:01:01.. We have used a highly informative technique for HLA typing of a Saudi healthy cohort to establish allele and haplotype frequencies. These results should prove useful for population studies, disease associations and future planning of the unrelated bone marrow donor registry.

Association of SNPs rs6498169 and rs10984447 with multiple sclerosis in Saudi patients: a model of the usefulness of familial aggregates in identifying genetic linkage in a multifactorial disease.

OBJECTIVE: Genome-Wide association studies (GWAS) showed an association between subset of single-nucleotide polymorphism (SNPs) and multiple sclerosis. Our study aims to study this association in Saudi familial multiple sclerosis patients. METHODS: Four subject groups were used in this study: sporadic MS (MS patients without family history), FMS (MS patients who have at least one family member diagnosed with MS), related controls (relatives of FMS patients who appear to be free of the disease) and independent controls (healthy volunteers). Subjects were genotyped for 15 SNPs. The variation in the genotype distribution was analyzed across study groups by using logistic regression. RESULTS: 342 subjects were included. 99 were in the sporadic MS group, 22 were FMS, 89 were related control, and 132 were independent control. SNPS rs3135388, rs7577363, rs1321172, rs6897932, rs6498169, rs12487066, and rs4763655were associated with MS when MS and independent control groups were compared. Same SNPS were identified but with stronger association when the FMS and independent control groups were compared. Finally, when the patients and the controls were selected from a much more homogenous genetic pool from which it would be expected that only SNPs highly linked to MS would persist, only two SNPs rs6498169[OR 4.26, CI (1.17 - 15.51)];, and rs10984447 [OR 13.63, CI(1.54, 120.83) ][were associated with MS. CONCLUSIONS: Our results suggest that using a more homogenous genetic pool of cases and controls could help to identify the most significant MS-associated SNPs. Our finding is in agreement with other studies including larger sample size and more diverse populations.