Copy number variation-based polymorphism in a new pseudoautosomal region 3 (PAR3) of a human X-chromosome-transposed region (XTR) in the Y chromosome

Veerappa, Avinash M.; Padakannaya, Prakash; Ramachandra, Nallur B.

doi:10.1007/s10142-013-0323-6

Cited by 45 publications

(46 citation statements)

References 20 publications

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“…This increased diversity cannot be attributed to mis-mapping between the X and Y as we only analyzed individuals with two X chromosomes (Methods). High diversity in the XTR contrasts with initial suggestions that there is no X-Y recombination in the XTR 12 , and is consistent with recent reports of X-Y recombination in some human populations in this region 46 .…”

Section: Resultssupporting

confidence: 88%

“…We observe that diversity is lower in the PAR2 than expected, and is not significantly different from the nonPAR region. We also show that diversity is elevated in the XTR above other nonPAR regions, verifying recent observations that the region may still undergo homologous recombination between the X and Y chromosomes 46 . Finally, when analyzing patterns of genetic diversity in windows across the human X chromosome we find that there is no strict boundary, based solely on the levels of diversity, between the recombining and putatively non-recombining regions, which could be attributed to the evolutionary shift in the PAB over time, extending the PAR1 due to a PAR1 length polymorphism 47 .…”

Section: Discussionsupporting

confidence: 90%

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Genetic diversity on the human X chromosome does not support a strict pseudoautosomal boundary

Cotter

Brotman

Wilson

2015

Preprint

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Unlike the autosomes, recombination between the X chromosome and Y chromosome often thought to be constrained to two small pseudoautosomal regions (PARs) at the tips of each sex chromosome. The PAR1 spans the first 2.7 Mb of the proximal arm of the human sex chromosomes, while the much smaller PAR2 encompasses the distal 320 kb of the long arm of each sex chromosome. In addition to the PAR1 and PAR2, there is a human-specific Xtransposed region that was duplicated from the X to the Y. The X-transposed region is often not excluded from X-specific analyses, unlike the PARs, because it is not thought to routinely recombine. Genetic diversity is expected to be higher in recombining regions than in nonrecombining regions because recombination reduces the effect of linked selection. In this study, we investigate patterns of genetic diversity in noncoding regions across the entire X chromosome of a global sample of 26 unrelated genetic females. We observe that genetic diversity in the PAR1 is significantly greater than the non-recombining regions (nonPARs). However, rather than an abrupt drop in diversity at the pseudoautosomal boundary, there is a gradual reduction in diversity from the recombining through the non-recombining region, suggesting that recombination between the human sex chromosomes spans across the currently defined pseudoautosomal boundary. In contrast, diversity in the PAR2 is not significantly elevated compared to the nonPAR, suggesting that recombination is not obligatory in the PAR2. Finally, diversity in the X-transposed region is higher than the surrounding nonPAR regions, providing evidence that recombination may occur with some frequency between the X and Y in the XTR.

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Section: Resultssupporting

confidence: 88%

Section: Discussionsupporting

confidence: 90%

Genetic diversity on the human X chromosome does not support a strict pseudoautosomal boundary

Cotter

Brotman

Wilson

2015

Preprint

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“…For example, UniProtKB P28068, HLA class II histocompatibility antigen, DM beta chain encoded by the HLA‐DMB gene has one primary and seven alternate mappings (https://www.ensembl.org/Human/Search/Results?q=P28068). (c) Homologous genes are found on pseudoautosomal regions of the X and Y chromosome (Helena Mangs & Morris, ; Veerappa, Padakannaya, & Ramachandra, ).…”

Section: Resultsmentioning

confidence: 99%

UniProt genomic mapping for deciphering functional effects of missense variants

et al. 2019

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Understanding the association of genetic variation with its functional consequences in proteins is essential for the interpretation of genomic data and identifying causal variants in diseases. Integration of protein function knowledge with genome annotation can assist in rapidly comprehending genetic variation within complex biological processes. Here, we describe mapping UniProtKB human sequences and positional annotations, such as active sites, binding sites, and variants to the human genome (GRCh38) and the release of a public genome track hub for genome browsers. To demonstrate the power of combining protein annotations with genome annotations for functional interpretation of variants, we present specific biological examples in disease‐related genes and proteins. Computational comparisons of UniProtKB annotations and protein variants with ClinVar clinically annotated single nucleotide polymorphism (SNP) data show that 32% of UniProtKB variants colocate with 8% of ClinVar SNPs. The majority of colocated UniProtKB disease‐associated variants (86%) map to 'pathogenic' ClinVar SNPs. UniProt and ClinVar are collaborating to provide a unified clinical variant annotation for genomic, protein, and clinical researchers. The genome track hubs, and related UniProtKB files, are downloadable from the UniProt FTP site and discoverable as public track hubs at the UCSC and Ensembl genome browsers.

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“…Some proteins and features map to multiple locations due to some gene families are indistinguishable at the protein level and some genes map to chromosomal regions with alternative assemblies. Examples of this include histones, MHC proteins and pseudoautosomal regions on both the X and Y chromosome (Helena Mangs and Morris 2007;Veerappa et al 2013). The data are provided in extended BED file and binary BigBed file formats on the UniProt FTP site in the genome_annotation_tracks directory.…”

Section: Resultsmentioning

confidence: 99%

UniProt Genomic Mapping for Deciphering Functional Effects of Missense Variants

McGarvey

Nightingale

Luo

et al. 2017

Preprint

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The integration of protein function knowledge in the UniProt Knowledgebase (UniProtKB) with genomic data provides unique opportunities for biomedical research by helping scientists to rapidly comprehend complex processes in biology. UniProtKB provides expert curation of functionally characterized variants reported in the literature, many of them associated with disease.Understanding the association of genetic variation with its functional consequences in proteins is essential for the interpretation of large-scale genomics data. UniProtKB protein sequences and sequence feature annotations such as active sites, modified sites, binding domains and amino acid variation have been mapped to the current build of the human genome (GRCh38). We have also created public track hubs for the Ensembl and UCSC browsers. We examine some specific biological examples in disease-related genes and proteins, illustrating the utility of combining protein and genome annotations for the functional interpretation of variants. We also present a larger comparison of UniProtKB variant and feature curation data that collocates with clinically observed SNP data from ClinVar, illustrating how protein and gene disease annotations currently compare and discuss some additional uses that might follow with combined annotation. The combination of gene and protein annotation can assist medical geneticists with the functional interpretation of variation. The genomic track hubs are downloadable from the UniProt FTP site (http://www.uniprot.org/downloads) and directly discoverable as public track hubs at the USCS and Ensembl genome browsers.

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Copy number variation-based polymorphism in a new pseudoautosomal region 3 (PAR3) of a human X-chromosome-transposed region (XTR) in the Y chromosome

Cited by 45 publications

References 20 publications

Genetic diversity on the human X chromosome does not support a strict pseudoautosomal boundary

Genetic diversity on the human X chromosome does not support a strict pseudoautosomal boundary

UniProt genomic mapping for deciphering functional effects of missense variants

UniProt Genomic Mapping for Deciphering Functional Effects of Missense Variants

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