Analysis of copy number variation at DMBT1 and age-related macular degeneration

BACKGROUND: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD. METHODS: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls. RESULTS: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD. CONCLUSIONS: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD

The Genetic Structure, Function and Relevance to Disease of The Salivary Agglutinin Gene (DMBT1)

Salivary agglutinin, encoded by the gene DMBT1, is a multifunctional high molecular mass glycoprotein (340 kDa) that acts as a pattern recognition receptor (PRRs) in innate immunity and mediates epithelial differentiation. The central region of the protein contains 13 tandemly-repeated scavenger receptor cysteine-rich (SRCR) domains that are copy number variable and bind to bacteria and viruses. The paralogue ratio test (PRT) was used to estimate the exact copy number of two distinct CNV (1 & 2) regions of DMBT1 gene and results were compared with other CNV estimation assays. Both CNV1 and CNV2 at DMBT1 were multiple allelic CNVs and diploid copy number varied in different populations. The de novo mutation rate at CNV1 and CNV2 of DMBT1 was estimated using a segregation study of 520 samples from 40 multigenerational CEPH families; a high mutation rate was found at both loci of DMBT1 (CNV1 - 1.4% and CNV2 - 3.3% per generation). The evolutionary basis of CNV at DMBT1 was examined using 971 samples from 52 populations from the Human Genome Diversity Panel (HGDP-CEPH). The study found that the subsistence history of human populations affected the frequency distribution of both CNVs at DMBT1. The increase in dental caries following the development of agriculture, and the likely causative role played by an increase in Streptococcus mutans following transition to a starch-rich diet, the present study suggests that this has favoured CNV1 and CNV2 alleles at DMBT1 with more S. mutans-binding SRCR domains in agricultural populations. Due to the functional importance of DMBT1, the study analysed association of DMBT1 copy number in different disease cohorts. The study found no evidence of the association between DMBT1 copy number with Crohn’s disease (n=2900), Urinary tract infection (UTI; n=405), vesicoureteral reflux (VUR; n=625), Chronic obstructive pulmonary disease (COPD; n=241) and Asthma cohorts (n=850). A significant association was found between CNV2 copy number and base-line HIV (n=987) viral load just before anti-retroviral therapy

Prevalence and molecular detection of tick borne pathogens in goats and ticks from different parts of North Eastern regions of India

Despite the fact that the climate of North-East (NE) India is suitable for tick diversity, no systematic study has been done regarding the prevalence of ticks and tick-borne pathogens affecting small ruminants. A total of 1053 goats belonging to different age groups, breeds, and sex were examined from April 2019 to March 2020. Blood smear examination and PCR assays were conducted to detect tick-borne pathogens in the collected samples. The tick species recorded were Rhipicephalus (Boophilus) microplus, Hyalomma anatolicum anatolicum, and Haemaphysalis bispinosa. The overall prevalence of tick-borne pathogens was 32.28. Mixed infection with Theileria sp. and Anaplasma sp. was most common followed by single infections of Anaplasma sp. and Theileria sp. A significantly higher rate of infection was observed in female animals. Species-specific PCR revealed different tickborne pathogens like Anaplasma marginale, Anaplasma centrale, and Theileria luwenshuni in goats. Isolated DNA samples of ticks were found to be positive for A. marginale, A. centrale, and T. luwenshuni and Coxiella burnetii in three genera of ticks with PCR assay. The results showed that vector-borne intracellular haemoprotozoa and Anaplasma are prevalent in the study area in apparently healthy small ruminants and the identified ticks have an endosymbiotic relationship with C. burnetii. © 2022 Informa UK Limited, trading as Taylor & Francis Group

Prolificacy in Raighar goats is independent of FecB gene

Aim: The Research was undertaken to find the association between FecB and high prolificacy in Raighar goats. Materials and Methods: DNA was extracted from blood, collected from does (n=101) with history of high prolificacy. Further tetra-primer amplification refractory mutation system (T-ARMS) PCR and agarose gel electrophoresis were followed to screen the mutation. Results: Raighar goats were found to be wild homozygotes suggesting absence of FecB mutation. Conclusion: Prolificacy in case of Raighar goats is not due to the mutation at FecB locus. It is thought to search for other genes or loci in goat fecundity. [Vet World 2013; 6(8.000): 479-481

Incidence of ecto-and endo-parasitic fauna in small wild ruminants from North Eastern region of India

The present study reports the prevalence of ecto- and endo- parasites in small wild ruminants from various NE region of India. A total of 565 wild small ruminants in captivity were examined between April 2018 to March 2019 without causing harm to them. Faecal samples were examined microscopically for detection of different Gastrointestinal (GI) parasites. Animals were also inspected visually for any ectoparasitic infestation and skin scrapping examination was also performed from suspected skin lesion for mite infestation. Overall seven species of endoparasites including three nematodes, two trematodes, one cestode and one protozoan parasite were recorded. The overall prevalence of GI parasites was 28.36%. Prevalence of Strongyle infection was found highest (11.5%) followed by infection with Moniezia spp (4.6%), Paramphistomum sp. (3.53%), Strongyloides spp (2.12%), Trichuris spp (1.77%) and Eurytrema sp. (1.59%) and Eimeria spp (3.25%), A significant difference was observed in wet season as compared to dry season. Similarly, a correlation was observed between sex and age. Female and young animals were more commonly infected than males and older animals. Among ectoparasites, we recorded three genera of hard ticks namely, Boophilus sp., Rhipicephalus sp. and Haemaphysalis sp. and one genius of mite belonging to the genus Psoroptes. The study clearly indicated that season, sex and age and other epidemiological factors play a significant role in parasitism in small wild ruminants. The possibility of cross transmission of parasites between livestock and wild life in NE region of India should deserve attention

Evolution of the rapidly mutating human salivary agglutinin gene (DMBT1) and population subsistence strategy.

The dietary change resulting from the domestication of plant and animal species and development of agriculture at different locations across the world was one of the most significant changes in human evolution. An increase in dietary carbohydrates caused an increase in dental caries following the development of agriculture, mediated by the cariogenic oral bacterium Streptococcus mutans. Salivary agglutinin [SAG, encoded by the deleted in malignant brain tumors 1 (DMBT1) gene] is an innate immune receptor glycoprotein that binds a variety of bacteria and viruses, and mediates attachment of S. mutans to hydroxyapatite on the surface of the tooth. In this study we show that multiallelic copy number variation (CNV) within DMBT1 is extensive across all populations and is predicted to result in between 7-20 scavenger-receptor cysteine-rich (SRCR) domains within each SAG molecule. Direct observation of de novo mutation in multigeneration families suggests these CNVs have a very high mutation rate for a protein-coding locus, with a mutation rate of up to 5% per gamete. Given that the SRCR domains bind S. mutans and hydroxyapatite in the tooth, we investigated the association of sequence diversity at the SAG-binding gene of S. mutans, and DMBT1 CNV. Furthermore, we show that DMBT1 CNV is also associated with a history of agriculture across global populations, suggesting that dietary change as a result of agriculture has shaped the pattern of CNV at DMBT1, and that the DMBT1-S. mutans interaction is a promising model of host-pathogen-culture coevolution in humans