A single amino acid deletion in the antigen binding site of BoLA-DRB3 is predicted to affect peptide binding

Two bovine MHC class II alleles, BoLA-DRB3*0201 and BoLA-DRB3*3301, contain a three base pair deletion which results in the deletion of a lysine (Kβ65) in the antigen recognition site (ARS). Modelling of BoLA-DRB3*0201 with the conserved lysine Kβ65 and BoLA-DRB3*0201 without Kβ65 indicated that this deletion altered the peptide specificity of the ARS, and may impact on the immune response. To test this hypothesis, the presence of Kβ65 was analysed in a sample of cattle vaccinated with the commercial cattle tick vaccine (TickGARD). Homozygous deletion of Kβ65 was significantly associated with high response to TickGARD (

Where does the gene for hemochromatosis lie in relation to HLA‐A?

Hereditary Hemochromatosis (HFE) is one of the most common inherited disorders with an estimated frequency of homozygous patients of 0.002‐0.0045. The disease is characterized by increased intestinal iron absorption and progressive iron overload. Affected subjects show clinical symptoms of parenchymal organ damage after the third‐fourth decade of life and have a 200‐fold increased risk of developing hepatocellular carcinoma. Early diagnosis and treatment prevent complications and may normalize life expectancy of patients. The biochemical and genetic defects leading to progressive iron accumulation are still unknown, but the HFE gene is tightly linked to HLA complex on the short arm of chromosome 6. Utilizing HLA serotypes and the study of several polymorphic markers of 6p21, a linkage analysis of the disease locus was performed in a series of Italian hemochromatosis families. The data obtained by linkage analysis and the study of a family with a double recombinant allowed us to better define the HFE gene location with respect to HLA‐class I A and F loci

A region of primer binding variation at the D6S265 locus associated with HLA-A25 and HLA-A26 antigens

Pyper, Wendy ; Burt, Michael ; Powell, Lawrie ; Webb, Sonja ; Adès, Lesley ; Halliday, June ; Jazwinska, Elizabet

Linkage disequilibrium analysis in Australian haemochromatosis patients indicates bipartite association with clinical expression

Background/Aims:Hereditary haemochromatosis shows a wide variation in phenotypic expression, which is thought to be due, in part, to genetic factors. A single missense mutation in HFE, leading to an amino acid substitution (C282Y) has been shown to be the causative mutation, clearly responsible for clinical expression of the disorder. Since homozygosity for the C282Y mutation can give rise to a disorder which shows wide variation in clinical expression, we investigated the possibility that genetic modifiers of HFE may exist. Methods: Linkage disequilibrium analysis was performed on chromosome 6p21,3 in 74 patients homozygous for the C282Y mutation using microsatellite markers spanning the haemochromatosis gene region. Phenotypic expression was evaluated based on transferrin saturation, serum ferritin, hepatic iron concentration and index, and iron grade. Results: Linkage disequilibrium (LD) analysis showed a predominant ancestral haplotype from D6S265 to D6S2236 covering a region of approximately 5 Mb. The overall LD distribution in this region showed two peaks of highly significant association at D6S105 (2 Mb proximal to HFE) and at D6S2239 approximately 50 kb distal to HFE. Male patients homozygous for D6S105 allele 8, had significantly higher hepatic iron indices than patients heterozygous or nullizygous for D6S105-8 (

The spinal muscular atrophy gene region at 5q13.1 has a paralogous chromosomal region at 6p21.3

Paralogous regions are duplicated segments of chromosomal DNA that have been acquired during the evolution of the genome. Subsequent divergent evolution of the genes within paralogous regions can lead to the formation of gene families. Here, we report the identification of a region on Chromosome (Chr) 6 at 6p21.3 that is paralogous with the Spinal Muscular Atrophy (SMA) gene region on Chr 5 at 5q13.1. Partial characterization of this region identified nine sequences all of which are highly homologous to DNA sequences of the SMA gene region at 5q13.1. These sequences include four beta-glucuronidase sequences, two retrotransposon sequences, a novel cDNA, a Sequence Tagged Site (STS), and one that is homologous to exon 9 of the Neuronal Apoptosis Inhibitor Protein (NAIP) gene. The 6p21.3 paralogous SMA region may contain genes that are related to those in the SMA region at 5q13.1; however, a direct association of this region with SR;IA is unlikely given that no linkage of SMA with Chr 6 has been reported