Evidence of uneven selective pressure on different subsets of the conserved human genome; implications for the significance of intronic and intergenic DNA

Davidson, Scott; Starkey, Andrew; MacKenzie, Alasdair

doi:10.1186/1471-2164-10-614

Cited by 23 publications

(18 citation statements)

References 32 publications

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“…Collectively, 951,507 biallelic SNPs (Coverage ≥10X and ≤60X) were predicted, with an estimated average genome-wide density of approximately 1.0 SNP/1.00 Kbp for the autosomes (i.e., Z and W excluded by blastn; Table S10). This estimate is higher than for the domestic turkey [16] and lower than for the zebra finch [17], with our estimate reflecting an overall average genome-wide autosomal distribution [41]–[42] as predicted by blastn. As expected, application of the same SNP detection methods [1] to the repeat-masked scaffolded de novo assembly (SMACv1.1, chicken and zebra finch repeat libraries), which contains N’s representing gaps, provided evidence for fewer biallelic SNPs (n = 890,527; Coverage ≥10X and ≤60X; Table S11), and a somewhat lower overall average SNP density.…”

Section: Resultscontrasting

confidence: 50%

A Multi-Platform Draft de novo Genome Assembly and Comparative Analysis for the Scarlet Macaw (Ara macao)

Seabury

Dowd²,

Seabury³

et al. 2013

PLoS ONE

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Data deposition to NCBI GenomesThis Whole Genome Shotgun project has been deposited at DDBJ/EMBL/GenBank under the accession AMXX00000000 (SMACv1.0, unscaffolded genome assembly). The version described in this paper is the first version (AMXX01000000). The scaffolded assembly (SMACv1.1) has been deposited at DDBJ/EMBL/GenBank under the accession AOUJ00000000, and is also the first version (AOUJ01000000). Strong biological interest in traits such as the acquisition and utilization of speech, cognitive abilities, and longevity catalyzed the utilization of two next-generation sequencing platforms to provide the first-draft de novo genome assembly for the large, new world parrot Ara macao (Scarlet Macaw). Despite the challenges associated with genome assembly for an outbred avian species, including 951,507 high-quality putative single nucleotide polymorphisms, the final genome assembly (>1.035 Gb) includes more than 997 Mb of unambiguous sequence data (excluding N’s). Cytogenetic analyses including ZooFISH revealed complex rearrangements associated with two scarlet macaw macrochromosomes (AMA6, AMA7), which supports the hypothesis that translocations, fusions, and intragenomic rearrangements are key factors associated with karyotype evolution among parrots. In silico annotation of the scarlet macaw genome provided robust evidence for 14,405 nuclear gene annotation models, their predicted transcripts and proteins, and a complete mitochondrial genome. Comparative analyses involving the scarlet macaw, chicken, and zebra finch genomes revealed high levels of nucleotide-based conservation as well as evidence for overall genome stability among the three highly divergent species. Application of a new whole-genome analysis of divergence involving all three species yielded prioritized candidate genes and noncoding regions for parrot traits of interest (i.e., speech, intelligence, longevity) which were independently supported by the results of previous human GWAS studies. We also observed evidence for genes and noncoding loci that displayed extreme conservation across the three avian lineages, thereby reflecting their likely biological and developmental importance among birds.

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Section: Resultscontrasting

confidence: 50%

A Multi-Platform Draft de novo Genome Assembly and Comparative Analysis for the Scarlet Macaw (Ara macao)

Seabury

Dowd²,

Seabury³

et al. 2013

PLoS ONE

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“…The remaining variation does not appear to contribute to an alloreactive mismatch. Introns might be expected to experience less selective pressure compared with protein‐encoding exons and therefore might exhibit more sequence variation; however, selective pressure may also conserve noncoding regions that control gene expression or impact sites in the vicinity of selected exon variants . The data presented here suggest that the introns will be highly conserved; further data on noncoding sequences will be needed to support this observation.…”

Section: Discussionmentioning

confidence: 78%

Limited HLA sequence variation outside of antigen recognition domain exons of 360 10 of 10 matched unrelated hematopoietic stem cell transplant donor‐recipient pairs

Hou

Vierra-Green

Lázaro

et al. 2016

HLA

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Traditional DNA-based typing focuses primarily on interrogating the exons of HLA genes that form the antigen recognition domain (ARD). The relevance of mismatching donor and recipient for HLA variation outside the ARD on hematopoietic stem cell transplantation (HCT) outcomes is unknown. This study was designed to evaluate the frequency of variation outside the ARD in 10/10 (HLA-A, -B, -C, -DRB1, -DQB1) matched unrelated donor transplant pairs (n=360). Next generation DNA sequencing was used to characterize both HLA exons and introns for HLA-A, -B, -C alleles; exons 2, 3 and the intervening intron for HLA-DRB1; and exons only for HLA-DQA1 and -DQB1. Over 97% of alleles at each locus were matched for their nucleotide sequence outside of the ARD exons. Of the 4320 allele comparisons overall, only 17 allele pairs were mismatched for non-ARD exons, 41 for noncoding regions and 9 for ARD exons. The observed variation between donor and recipient usually involved a single nucleotide difference (88% of mismatches); 88% of the non-ARD exon variants impacted the amino acid sequence. The impact of amino acid sequence variation caused by substitutions in exons outside ARD regions in D-R pairs will be difficult to assess in HCT outcome studies since these mismatches do not occur very frequently.

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“…ERa gene polymorphisms described here are located in intron 1; however, it is not clear how intronic polymorphisms could affect cartilage metabolism. There is recent evidence that in human genome, intronic and exonic portions have been subjected to the same degree of selective pressure, and that the intronic portion possesses a similar level of functional importance to that of the exonic [19]. Therefore, intronic polymorphisms could have functional consequences in OA.…”

Section: Discussionmentioning

confidence: 94%

Analysis of estrogen receptor alpha gene haplotype in Mexican mestizo patients with primary osteoarthritis of the knee

et al. 2011

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The aim of this work was to test the association between estrogen receptor α gene (ERα) polymorphism and primary osteoarthritis (OA) of the knee in Mexican mestizo patients. A case-control study was conducted. Cases were patients >40 years of age, with a body mass index (BMI) ≤ 27 and radiologic score for OA of the knee of ≥2 according to Kellgren-Lawrence scale, and controls were subjects >40 years age with a radiologic score <2. Two restriction fragment length polymorphisms, PvuII (T/C; rs2234693), and XbaI (A/G; rs9340799), of the ERα were analyzed. Allelic haplotypes were constructed and non-conditional logistic regression was developed to evaluate risk magnitude through odds ratios (ORs) and 95% Confidence intervals (95% CI). Three different allelic haplotypes were identified: TA; CG, and CA. Unadjusted analysis of the haplotypes did not show significant associations; nonetheless, when data were adjusted for gender, age, and BMI, a significant decrease risk was observed for CG haplotype (OR [95% CI]) = 0.5 (0.3-0.9)] (P = 0.04). These results suggest that ERα gene CG haplotype could be associated with a reduced risk of primary knee OA in Mexican mestizo population.

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Evidence of uneven selective pressure on different subsets of the conserved human genome; implications for the significance of intronic and intergenic DNA

Cited by 23 publications

References 32 publications

A Multi-Platform Draft de novo Genome Assembly and Comparative Analysis for the Scarlet Macaw (Ara macao)

A Multi-Platform Draft de novo Genome Assembly and Comparative Analysis for the Scarlet Macaw (Ara macao)

Limited HLA sequence variation outside of antigen recognition domain exons of 360 10 of 10 matched unrelated hematopoietic stem cell transplant donor‐recipient pairs

Analysis of estrogen receptor alpha gene haplotype in Mexican mestizo patients with primary osteoarthritis of the knee

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