Tandem Repeat Polymorphisms

Hannan, Anthony J.

doi:10.1007/978-1-4614-5434-2_1

Cited by 21 publications

(10 citation statements)

References 61 publications

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“…Another important source of sequence variation is the heterogeneity in the copy numbers of adjacently repeated elements or tandem repeats (TRs), caused by recombination or strand slippage replication. Variation in TRs is associated with phenotypic variability, regulation of gene expression, and genetic evolvability in both prokaryotes and eukaryotes (74)(75)(76). Furthermore, several studies have found evidence that TR variations may impact strain functionality and pathogenicity in viruses (77)(78)(79)(80)(81)(82).…”

Section: Resultsmentioning

confidence: 99%

High-Throughput Analysis of Human Cytomegalovirus Genome Diversity Highlights the Widespread Occurrence of Gene-Disrupting Mutations and Pervasive Recombination

Sijmons

Thys

Ngwese

et al. 2015

J Virol

159

219

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Human cytomegalovirus is a widespread pathogen of major medical importance. It causes significant morbidity and mortality in immunocompromised individuals, and congenital infections can result in severe disabilities or stillbirth. Development of a vaccine is prioritized, but no candidate is close to release. Although correlations of viral genetic variability with pathogenicity are suspected, knowledge about the strain diversity of the 235-kb genome is still limited. In this study, 96 full-length human cytomegalovirus genomes from clinical isolates were characterized, quadrupling the amount of information available for full-genome analysis. These data provide the first high-resolution map of human cytomegalovirus interhost diversity and evolution. We show that cytomegalovirus is significantly more divergent than all other human herpesviruses and highlight hot spots of diversity in the genome. Importantly, 75% of strains are not genetically intact but contain disruptive mutations in a diverse set of 26 genes, including the immunomodulatory genes UL40 and UL111A. These mutants are independent of culture passage artifacts and circulate in natural populations. Pervasive recombination, which is linked to the widespread occurrence of multiple infections, was found throughout the genome. The recombination density was significantly higher than those of other human herpesviruses and correlated with strain diversity. While the overall effects of strong purifying selection on virus evolution are apparent, evidence of diversifying selection was found in several genes encoding proteins that interact with the host immune system, including UL18, UL40, UL142, and UL147. These residues may present phylogenetic signatures of past and ongoing virus-host interactions. IMPORTANCEHuman cytomegalovirus has the largest genome of all viruses that infect humans. Currently, there is a great interest in establishing associations between genetic variants and strain pathogenicity of this herpesvirus. Since the number of publicly available full-genome sequences is limited, knowledge about strain diversity is highly fragmented and biased toward a small set of loci. Combined with our previous work, we have now contributed 101 complete genome sequences. We have used these data to conduct the first high-resolution analysis of interhost genome diversity, providing an unbiased and comprehensive overview of cytomegalovirus variability. These data are of major value to the development of novel antivirals and a vaccine and to identify potential targets for genotype-phenotype experiments. Furthermore, these data have enabled a thorough study of the evolutionary processes that have shaped cytomegalovirus diversity. Human cytomegalovirus (HCMV), the prototype member of the herpesvirus subfamily Betaherpesvirinae, is a widespread and important pathogen. Seroprevalence in the adult population ranges from 45% to 100% (1). After primary infection, HCMV establishes a lifelong, latent infection in myeloid progenitor cells (2). This virus causes mild to ...

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Section: Resultsmentioning

confidence: 99%

High-Throughput Analysis of Human Cytomegalovirus Genome Diversity Highlights the Widespread Occurrence of Gene-Disrupting Mutations and Pervasive Recombination

Sijmons

Thys

Ngwese

et al. 2015

J Virol

159

219

View full text Add to dashboard Cite

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“…This however, does not imply contradiction with reports on genome size and repeat correlation, but indicates that repeat density may vary in different genes and may show characteristic deviations in the keratin genes from the overall genome pattern. It is possible that the human hair keratin genes have repeats for some functional reasons as studies have suggested importance of repeats in different genes 19,23,25,30,31,38,[42][43][44][45][46][47][48][49]64 . The present study shows few trinucleotide repeats; and dinucleotide repeats are not as abundant as tetra-and mono-nucleotide repeats.…”

Section: Discussionmentioning

confidence: 99%

“…Expansion or contraction of SSRs generally happens during DNA replication and is frequent on the lagging strand 21,[26][27][28][29] . SSR length mutations may modify genes 21,30,31 and or cause disorders whether repeats are present in exons, introns or un-transcribed regions 23,[32][33][34][35][36][37][38][39][40] . Triplet repeat expansions can also lead to non-ATG (RAN) translation i.e.…”

Section: Introductionmentioning

confidence: 99%

“…However, SSRs may have functional roles 23,25,30,38,[42][43][44][45] . Selection of microsatellites can affect linked gene diversity 46 , genome diversity 47 , influence evolution 19,30,31,38,48 , rate of evolution of sequences (gene) 49 , adaptability to changing environmental conditions 25 , brain development and function 38 etc.…”

Section: Introductionmentioning

confidence: 99%

“…Selection of microsatellites can affect linked gene diversity 46 , genome diversity 47 , influence evolution 19,30,31,38,48 , rate of evolution of sequences (gene) 49 , adaptability to changing environmental conditions 25 , brain development and function 38 etc. SSRs can also influence phenotype or behaviour at individual and interspecies level as seen in study on vasopressin avpr1a gene in voles (Microtus), homologue in humans, bonobos (Pan paniscus) and chimp (Pan troglodytes) 30 .…”

Section: Introductionmentioning

confidence: 99%

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Few Simple Sequence Repeats in Human Hair

2017

JCBSC

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Abstract:Keratin genes are subgroup of intermediate filament (IF) genes. Keratins expressed in hair are called "hair keratins". Comparison of keratin gene sequences and structural organization has been done earlier but no study has been undertaken that compares human hair keratin genes with orthologues in chimp, orangutan, macaque and platypus, with specific references to simple sequence repeats (SSRs) or microsatellites. This study seeks presence of SSRs in human hair keratin genes and compares their positions in orthologue genes. Although the structural organization of keratin genes is largely conserved, as reported in other studies; some human keratin genes show differences in the number of exons and the lengths of exons/introns, when compared with the orthologues. The present study shows few SSRs in human hair keratin genes, where only one repeat is found in exon of Type I keratin gene KRT31, while additional repeats are present in introns. Some repeats are longer in the human genes whereas some indicate reduction in length compared with orthologues. Many repeats are present in regions that are known for intronic variations. This study revisits the comparisons of structural organization of human hair keratin genes and compares them with the orthologues. The SSRs found here could be useful for monitoring variations in human hair keratin genes that may happen due to hypermutable nature of SSRs.

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