Biology subjects

Oketch, J. W.

Publications and source records attributed to Oketch, J. W..

3 recordsLinked to original sources

bioRxiv2024

β-defensin gene copy number variation in cattle

{beta}-defensins are peptides with antimicrobial roles, characterized by a conserved tertiary structure. Beyond antimicrobial functions, they exhibit diverse roles in both the immune response and fertility, including involvement in sperm maturation and function. Copy number variation (CNV) of {beta}-defensin genes is extensive across mammals, including cattle, with possible implications for reproductive traits and disease resistance. In this study, we comprehensively catalogue 55 {beta}-defensin genes in cattle. By constructing a phylogenetic tree to identify human orthologues and lineage-specific expansions, we identify 1:1 human orthologues for 35 bovine {beta}-defensins. We also discover extensive {beta}-defensin gene CNV across breeds, with DEFB103 in particular showing extensive multiallelic CNV. By comparing {beta}-defensin expression levels in testis from calves and adult bulls, we find that 14 {beta}-defensins, including DEFB103, increase in expression during sexual maturation. Analysis of {beta}-defensin gene expression levels in the caput of adult bull epididymis, and {beta}-defensin gene copy number, in 94 matched samples shows expression level of four {beta}-defensins are correlated with genomic copy number, including DEFB103. We therefore demonstrate extensive copy number variation in bovine {beta}-defensin genes, in particular DEFB103, with potential functional consequences for fertility.

genetics↗

bioRxiv2022

A comparison of software for analysis of rare and common short tandem repeat (STR) variation using human genome sequences from clinical and population-based samples

Short tandem repeat (STR) variation is an often overlooked source of variation between genomes. STRs comprise about 3% of the human genome and are highly polymorphic. Some cause Mendelian disease, and others affect gene expression. Their contribution to common disease is not well-understood, but recent software tools designed to genotype STRs using short read sequencing data are beginning to address this. Here, we compare software that genotypes common STRs and rarer STR expansions genome-wide, with the aim of applying them to population-scale genomes. By using the Genome-In-A-Bottle (GIAB) consortium and 1000 Genomes Project sequencing data, we compare performance in terms of sequence length, depth, computing resources needed, genotyping accuracy and number of STRs genotyped. To ensure broad applicability of our findings, we also measure genotyping performance against a set of genomes from clinical samples with known STR expansions, and a set of STRs commonly used for forensic identification. We find that HipSTR, ExpansionHunter and GangSTR perform well in genotyping common STRs, including the CODIS 13 core STRs used for forensic analysis. GangSTR and ExpansionHunter outperform HipSTR for genotyping call rate and memory usage. ExpansionHunter denovo (EHdn), STRling and GangSTR outperformed STRetch for detecting expanded STRs, and EHdn and STRling used considerably less processor time compared to GangSTR. Analysis on shared genomic sequence data provided by the GIAB consortium allows future performance comparisons of new software approaches on a common set of data, facilitating comparisons and allowing researchers to choose the best software that fulfils their needs.

genomics↗

bioRxiv2018

Whole genome analysis of local Kenyan and global sequences unravels the epidemiological and molecular evolutionary dynamics of RSV genotype ON1 strains

The respiratory syncytial virus (RSV) group A variant with the 72-nucleotide duplication in the G gene, genotype ON1, was first detected in Kilifi in 2012 and has almost completely replaced previously circulating genotype GA2 strains. This replacement suggests some fitness advantage of ON1 over the GA2 viruses, and might be accompanied by important genomic substitutions in ON1 viruses. Close observation of such a new virus introduction over time provides an opportunity to better understand the transmission and evolutionary dynamics of the pathogen. We have generated and analyzed 184 RSV-A whole genome sequences (WGS) from Kilifi (Kenya) collected between 2011 and 2016, the first ON1 genomes from Africa and the largest collection globally from a single location. Phylogenetic analysis indicates that RSV-A transmission into this coastal Kenya location is characterized by multiple introductions of viral lineages from diverse origins but with varied success in local transmission. We identify signature amino acid substitutions between ON1 and GA2 viruses within genes encoding the surface proteins (G, F), polymerase (L) and matrix M2-1 proteins, some of which were identified as positively selected, and thereby provide an enhanced picture of RSV-A diversity. Furthermore, five of the eleven RSV open reading frames (ORF) (i.e. G, F, L, N and P), analyzed separately, formed distinct phylogenetic clusters for the two genotypes. This might suggest that coding regions outside of the most frequently studied G ORF play a role in the adaptation of RSV to host populations with the alternative possibility that some of the substitutions are nothing more than genetic hitchhikers. Our analysis provides insight into the epidemiological processes that define RSV spread, highlights the genetic substitutions that characterize emerging strains, and demonstrates the utility of large-scale WGS in molecular epidemiological studies.\n\nAuthor summaryRespiratory syncytial virus (RSV) is the leading viral cause of severe pneumonia and bronchiolitis among infants and children globally. No vaccine exists to date. The high genetic variability of this RNA virus, characterized by group (A or B), genotype (within group) and variant (within genotype) replacement in populations, may pose a challenge to effective vaccine design by enabling immune response escape. To date most sequence data exists for the highly variable G gene encoding the RSV attachment protein, and there is little globally-sampled RSV genomic data to provide a fine resolution of the epidemiology and evolutionary dynamics of the pathogen. Here we use long-term RSV surveillance in coastal Kenya to track the introduction, spread and evolution of a new RSV genotype known as ON1 (having a 72-nucleotide duplication in the G gene). We present a set of 184 RSV-A whole genomes, including 176 of RSV ON1 (the first from Africa), describe patterns of local ON1 spread and show genome-wide changes between the two major RSV-A genotypes that may define the pathogens adaptation to the host. These findings have implications for vaccine design and improved understanding of RSV epidemiology and evolution.

epidemiology↗