SEARCH · Search PubMed

Results for “synonymous mutation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources

PubMed1994

Mutation in the human gene for 3 beta-hydroxysteroid dehydrogenase type II leading to male pseudohermaphroditism without salt loss.

A 5-year-old XY pseudohermaphrodite was found to have a defect of steroid biosynthesis consistent with a partial deficiency of the enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). Circulating concentrations of delta 5 steroids and delta 5 urinary steroid metabolites were elevated and remained elevated after orchidectomy. There was no evidence of salt loss, plasma renin being within normal limits, and no detectable glucocorticoid abnormality. The coding sequences of the genes for 3 beta-HSD types I and II were amplified by PCR and screened for mutations by denaturing gradient gel electrophoresis (DGGE) and manual and automatic DNA sequencing. A mutation in the gene for 3 beta-HSD type II was observed at codon 173 (CTA-->CGA), leading in the affected patient to a homozygous substitution in which the leucine at residue 173 was altered to an arginine (L173R). The propositus's 2-year-old XX sister was also homozygous for L173R and showed the biochemical characteristics of partial 3 beta-HSD deficiency without clinical symptoms or signs. The mutation segregated as an autosomal recessive. Three related heterozygous adult females showed evidence of a small over-production of delta 5 steroids and steroid metabolites and a variable reduction in ovarian function. Concentrations of delta 5 steroids and steroid metabolites in the heterozygous father of the propositus were within the normal range. These data are discussed in relation to the endocrine causes of pseudohermaphroditism and hirsutism. Evidence for tight linkage between the genes for 3 beta-HSD types I and II was obtained using a microsatellite polymorphism in the third intron of the gene for 3 beta-HSD type II and synonymous and non-synonymous mutations and polymorphisms in the gene for 3 beta-HSD type I. The latter polymorphisms were located 88 bp apart at the 3' end of the type I coding sequence and could be physically resolved as haplotypes using DGGE. The application of DGGE to the analysis of mutations in members of a multigene family is discussed.

3-Hydroxysteroid Dehydrogenases↗

PubMed2003

Increased variation in mtDNA in patients with familial sensorineural hearing impairment.

Analyses of mitochondrial DNA (mtDNA) sequences have revealed non-neutral patterns, suggesting that many amino acid mutations in animal mtDNA may be mildly deleterious, but this has not been verified in human clinical series. Since sensorineural hearing impairment (SNHI) is a common manifestation in many of the syndromes caused by mutations in mtDNA, this may be regarded as the phenotype of choice in attempts to detect mutations that may have a mildly deleterious effect on mitochondrial function. We selected 32 subjects from among 117 unrelated SNHI patients with SNHI in maternal relatives by means of family history, determined the entire coding region sequence of mtDNA and compared the sequence variation with that in 32 haplogroup-matched controls taken at random from 192 Finnish sequences. The 32 control sequences differed from the remaining 160 sequences by 36+/-9 substitutions (mean +/- SD), while the difference for the 32 patients was 58+/-4 substitutions ( P=0.005 for difference; Wilcoxon signed rank test). Differences were also found in the number of new haplotypes and new non-synonymous mutations or mutations in tRNA or rRNA genes. A total of 12 rare mtDNA variants were detected in the patients, and only 3 of these were considered to be neutral in effect. It is proposed that increased sequence variation in mtDNA may be a genetic risk factor for SNHI, and the increased frequency of rare haplotypes in these patients points to the presence of mildly deleterious mutations in mtDNA.

Adenine↗

PubMed2003

A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome.

Seckel syndrome (OMIM 210600) is an autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly and mental retardation. Clinically, Seckel syndrome shares features in common with disorders involving impaired DNA-damage responses, such as Nijmegen breakage syndrome (OMIM 251260) and LIG4 syndrome (OMIM 606593). We previously mapped a locus associated with Seckel syndrome to chromosome 3q22.1-q24 in two consanguineous Pakistani families. Further marker analysis in the families, including a recently born unaffected child with a recombination in the critical region, narrowed the region to an interval of 5 Mbp between markers D3S1316 and D3S1557 (145.29 Mbp and 150.37 Mbp). The gene encoding ataxia-telangiectasia and Rad3-related protein (ATR) maps to this region. A fibroblast cell line derived from an affected individual displays a defective DNA damage response caused by impaired ATR function. We identified a synonymous mutation in affected individuals that alters ATR splicing. The mutation confers a phenotype including marked microcephaly (head circumference 12 s.d. below the mean) and dwarfism (5 s.d. below the mean). Our analysis shows that UV-induced ATR activation can occur in non-replicating cells following processing by nucleotide excision repair.

Ataxia Telangiectasia Mutated Proteins↗

PubMed2001

A malignant phenotype of hypertrophic cardiomyopathy caused by Arg719Gln cardiac beta-myosin heavy-chain mutation in a Chinese family.

Mutations of the cardiac beta-myosin heavy-chain (beta-MHC) gene cause hypertrophic cardiomyopathy (HCM). Recent genotype-phenotype correlation studies have shown that mutations carry prognostic significance. We studied five unrelated Chinese families with hypertrophic cardiomyopathy. Exons 3-27 and 40 of the beta-MHC gene were screened with both the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method and the cycle sequencing of the PCR products. A previously reported heterozygous mutation Arg719Gln (arginine-->glutamine in codon 719) in exon 19 was found in one family. The proband is a 30-year-old female diagnosed at age of 25 years when she presented with symptoms of chest pain, palpitations, and frequent incidents of dizziness and syncope. A two-dimensional echocardiogram showed moderate asymmetrical septal hypertrophy with left atrial enlargement. There was no obstruction of the left ventricular outflow tract (LVOT). The patient also developed atrial fibrillation. The proband's mother and one of her sisters had similar clinical manifestations and both died suddenly at the age of 38 years. In addition, two silent nucleotide substitutions (ACT63ACC, TTT244TTC) in the cardiac beta-MHC gene were identified in the other four families. These synonymous mutations did not cosegregate with the disease in the families and they were also present in the 60 healthy and age-matched control subjects. Of the five families studied, we did not find any missense mutation in the remaining four families. The missense mutation Arg719Gln found in the Chinese family is associated with a malignant phenotype of severe clinical symptoms and poor survival prognosis. This mutation also causes atrial enlargement and atrial fibrillation. Our study provides further evidence that the mutation, which alters the charge of the myosin heavy chain, is associated with a serious clinical outcome.

Adult↗

PubMed1993

Rapid sequence evolution of the mammalian sex-determining gene SRY.

In mammals, induction of male sex determination requires the Y-chromosome gene SRY. SRY encodes a protein with a central 'high mobility group' domain (HMG box) of about 78 amino acids. HMG boxes are found in a wide variety of proteins that bind to DNA with high affinity but differing degrees of sequence specificity. The human SRY protein binds to linear DNA with sequence specificity and to cruciform DNA structures without sequence specificity. The DNA-binding activity of the SRY protein resides in the HMG box and mutations in this region are associated with sex reversal in XY females. No function has been ascribed to the portions of the SRY protein outside the HMG box. SRY belongs to a family of genes that are related by sequence homology within the DNA-binding domain: the genes most similar to SRY (> 60%) have been named SOX genes (SRY box genes). None of the known SOX genes is homologous to SRY outside the HMG-box region. Although SRY is an important developmental regulator, its sequence is poorly conserved between species apart from the HMG-box domain. Here we investigate the coding sequence of SRY in primates and find that evolution has been rapid in the regions flanking the conserved domain. The high degree of sequence divergence and the frequency of non-synonymous mutations suggest either that the majority of the coding sequence has no functional significance or that directional selection has occurred.

Amino Acid Sequence↗

PubMed2003

[Study on gene mutations of alpha-thalassemia in the South of China].

There is a high prevalence of thalassemia in the South of China. To explore the genotype of alpha-thalassemia as well as the distribution of alpha globin gene mutation in the South of China, 356 patients with heterozygote alpha(+) thalassemia, heterozygote alpha(0) or homozygote alpha(+) thalassemia and 78 patients with HbH were analyzed. The gene diagnosis methods including Gap-PCR, nested-PCR, PCR-RE, PCR-SSCP, 4P-ASPCR and DNA sequence analysis were used. The results showed that among 356 patients, 295 patients with --SEA/alphaalpha (82.87%), 1 patient with alphaalpha/alpha-alpha(3.7) (0.28%), 3 patients with alphaalpha/alpha-alpha(4.2) (0.84%), 3 patients with alphaalpha/alpha(CS)alpha (0.84%), 1 patient with alphaalpha/alphaalpha(QS) (0.28%) and 2 patients with alphaalpha/alpha(Westmead) alpha (0.56%) were found. The homozygote with -alpha(4.2) or -alpha(3.7) was not found. In 78 patients with HbH, 29 patients with --SEA/alphaalpha(-3.7) (37.2%), 20 patients with --SEA/alphaalpha(-4.2) (25.6%), 19 patients with --SEA/alphaalpha(CS) (24.3%), 2 patients with --SEA/alphaalpha(QS) (2.6%) were detected, and other remaiming 8 patients were needed to be defined. Among the non-defined 8 patients, the synonymous mutation with C-->G transversion (GCC-GCG) at codon 65 in the exon 2 of alpha 2-globin gene was detected in 2 unrelated HbH patients came from Guangxi province. Whether it correlated with the phenotype of HbH disease or it is only a single nucleotide polymorphism site (SNPs), should be confirmed in the future. In addition, a set of gene diagnosis methods based on PCR to screen deletion and non-deletion genotypes of alpha-thalassemia in Chinese was improved. A new method, 4P-ASPCR, to detect Hb CS and Hb QS was also developed. The method was verified to be more accurate, time-saving and economic. In conclusion, the genotypes of alpha-thalassemia in Chinese are very complicated, the genotypes of alpha-thalassemia in Chinese need to be further studied, the results of this research probably have practical significance for the gene diagnosis or antenatal diagnosis of alpha-thalassemia in the South of China.

Base Sequence↗

PubMed2003

The rat STSL locus: characterization, chromosomal assignment, and genetic variations in sitosterolemic hypertensive rats.

BACKGROUND: Elevated plant sterol accumulation has been reported in the spontaneously hypertensive rat (SHR), the stroke-prone spontaneously hypertensive rat (SHRSP) and the Wistar-Kyoto (WKY) rat. Additionally, a blood pressure quantitative trait locus (QTL) has been mapped to rat chromosome 6 in a New Zealand genetically hypertensive rat strain (GH rat). ABCG5 and ABCG8 (encoding sterolin-1 and sterolin-2 respectively) have been shown to be responsible for causing sitosterolemia in humans. These genes are organized in a head-to-head configuration at the STSL locus on human chromosome 2p21. METHODS: To investigate whether mutations in Abcg5 or Abcg8 exist in SHR, SHRSP, WKY and GH rats, we initiated a systematic search for the genetic variation in coding and non-coding region of Abcg5 and Abcg8 genes in these strains. We isolated the rat cDNAs for these genes and characterized the genomic structure and tissue expression patterns, using standard molecular biology techniques and FISH for chromosomal assignments. RESULTS: Both rat Abcg5 and Abcg8 genes map to chromosome band 6q12. These genes span ~40 kb and contain 13 exons and 12 introns each, in a pattern identical to that of the STSL loci in mouse and man. Both Abcg5 and Abcg8 were expressed only in liver and intestine. Analyses of DNA from SHR, SHRSP, GH, WKY, Wistar, Wistar King A (WKA) and Brown Norway (BN) rat strains revealed a homozygous G to T substitution at nucleotide 1754, resulting in the coding change Gly583Cys in sterolin-1 only in rats that are both sitosterolemic and hypertensive (SHR, SHRSP and WKY). CONCLUSIONS: The rat STSL locus maps to chromosome 6q12. A non-synonymous mutation in Abcg5, Gly583Cys, results in sitosterolemia in rat strains that are also hypertensive (WKY, SHR and SHRSP). Those rat strains that are hypertensive, but not sitosterolemic (e.g. GH rat) do not have mutations in Abcg5 or Abcg8. This mutation allows for expression and apparent apical targeting of Abcg5 protein in the intestine. These rat strains may therefore allow us to study the pathophysiological mechanisms involved in the human disease of sitosterolemia.

Animals↗

PubMed2006

Sub-Saharan African coding sequence variation and haplotype diversity at the NAT2 gene.

A total of 530 chromosomes from 12 sub-Saharan African populations were sequenced at the human arylamine N-acetyltransferase NAT2 gene. We identified seven novel non-synonymous mutations observed at low frequencies (<11%) in our African multi-ethnic panel. By using algorithms based on evolutionary conservation, two mutations (c.70T>A [p.L24I] and c.578C>T [p.T193M]) for which the activity of their encoded protein has never been determined, were predicted to entail a potentially damaging effect on protein activity. In addition, approximately 5% of the overall NAT2 African haplotypes presented an unknown functional effect. More interestingly, NAT2 haplotype frequencies and acetylation status inference revealed that the hunter-gatherer Western Pygmies and !Kung San were mainly composed of fast and intermediate acetylators, in clear contrast with most agriculturalist populations. These observations highlight the need of a detailed genetic characterization of African populations at this locus to adapt medical treatment, such as the antitubercular isoniazid, to individual/population make-up in the most effective manner.

Africa South of the Sahara↗

PubMed2004

Genetic variation in clinical varicella-zoster virus isolates collected in Ireland between 2002 and 2003.

Analysis of genetic variation in 16 varicella-zoster virus (VZV) isolates selected at random and circulating in the Irish population between March 2002 and February 2003 was carried out. A 919 bp fragment of the glycoprotein E gene (open reading frame 68) encompassing codon 150, at which a non-synonymous mutation defines the escape mutant VZV-MSP, and including two other epitope regions e1 and c1, was sequenced. No new single nucleotide polymorphisms (SNPs) were detected, indicating stability of these epitopes in clinical isolates of VZV. However, when four informative polymorphic markers consisting of defined regions from genes 1, 21, 50, and 54 were sequenced 14 variable nucleotide positions were identified. Phylogenetic analysis showed the presence of three highly supported clades A, B, and C circulating in the Irish population. Approximately one third (6/16; 37.5%) of the Irish VZV isolates in this study belonged to genotype C, 4/16 (25%) to genotype A, and 4/16 (25%) to genotype B. A smaller number 2/16 (12.5%) belonged to genotype J1. This indicates remarkable heterogeneity in the Irish population given the small sample size. No evidence was found to suggest any of the 16 isolates was a recombinant. These findings have implications for the model of geographic isolation of VZV clades to certain regions as the circulating Irish VZV population appears to comprise approximately equal numbers of each of the main genotypes. This data is inconsistent with a model of strict geographical separation of VZV genotypes and suggests that VZV diversity is more pronounced in certain areas than had been thought previously.

Adult↗

PubMed2004

Molecular and serological evaluation of surface antigen negative hepatitis B virus infection in blood donors from Venezuela.

Surface antigen negative hepatitis B virus (HBV) infection was evaluated in Venezuela, by molecular characterization of blood samples positive for antibodies to core antigen (anti-HBc) and negative for surface antigen (HBsAg) in blood donors (residual infections). HBV DNA was found in 11/258 samples (4.3%), and was significantly associated with high levels of anti-HBc antibodies (>25 UI/ml, P < 0.05), while no correlation was found between the presence of HBV DNA and the levels of anti-HBs. Synonymous and non-synonymous mutations were found in the HBV surface region (but not vaccine escape mutants) and in the precore/core region (precore mutants in 2/7 samples and 33-45 bp deletions near the N-terminal core region in 4/19 samples). While HBV genotype F prevails among HBsAg positive samples from blood donors in Venezuela, residual infection isolates were mainly genotypes A and D. Phylogenetic analysis of viral surface and core region revealed discrepancies in genotype designation in 6/9 samples, suggesting the presence of mixed infection or recombination. In conclusion, HBV residual infection in Venezuela does not seem to be frequently observed in HBV genotype F. This type of infection is frequently associated with variants exhibiting mutations in the surface gene that might be affecting the correct recognition by commercial tests, with precore mutants and with core internal deletions. These variants do not seem to cause severe liver disease, and on the contrary, were found circulating at low viremia.

Amino Acid Sequence↗

PubMed2025

Impact of High-Titer Convalescent Plasma on Clinical and Virologic Outcomes Among Veterans Hospitalized With SARS-CoV-2 Infection: VA CoronavirUs Research and Efficacy Studies-1 (VA CURES-1).

In the initial absence of proven therapies, empirical COVID-19 convalescent plasma (CCP) was rapidly introduced for individuals hospitalized for COVID-19. Seventy-five participants were randomized from November 2020 to June 2021 in a double-blind, multi-site, placebo-controlled, randomized trial (VA CURES-1) evaluating the impact of CCP vs. saline in Veterans hospitalized with COVID-19 with hypoxemia. The composite primary outcome was acute hypoxemic respiratory failure or all-cause death by Day 29. We analyzed clinical outcomes, nasal viral RNA, plasma cytokines and viral evolution over time. Among 40 participants receiving saline and 35 receiving CCP with high neutralizing titers (median 1:1420), the percent reaching the primary outcome was similar (10%), as were time to clinical recovery and to nasal viral clearance. By whole genome sequencing, viral molecular complexity evolved pre- to posttreatment more frequently in recipients of saline vs. CCP (4 of 7 (57.1%) vs. 1 of 4 (25%), respectively), based on numbers of mixed allele positions. Numbers of amino acid-changing, non-synonymous mutations in the spike protein were greater in saline vs. CCP recipients. Both outcomes suggested purifying selection (reduced overall viral infection complexity) following CCP. In conclusion, convalescent plasma showed no significant clinical impact but may influence SARS-CoV-2 complexity. Trial Registration: ClinicalTrials.gov Identifier: NCT04539275.

Aged↗

PubMed1995

Genetic polymorphism in the rabies virus nucleoprotein gene.

In an attempt to compare intrinsic and extrinsic genetic diversity of the lyssavirus genotypes, 69 rabies virus isolates from various part of the world were partially sequenced and compared to 13 representative isolates of the 6 lyssavirus genotypes. The analysis of their phylogenetic relationships, performed on the complete nucleoprotein (N) coding gene (1350 bases), established that the rabies virus isolates all belonged to genotype 1 and that at least 11 phylogenetic lineages could be identified in accordance with their geographical localization and species of origin. These lineages diverged mostly by the accumulation of synonymous mutations. Stabilizing selection, possibly related to host specificity, limits amino acid sequence and antigenic drift. Analyses were also performed either on the highly variable 400-base region coding for the amino terminus of the N protein or on the 93-base noncoding region corresponding to the 3' end of the N mRNA, the intergenic N-phosphoprotein (M1) region, and the 5' end of the M1 mRNA. These shorter nucleotide sequences were shown to provide phylogenetic data suitable for the completion of large epidemiological studies, but with less robustness. This latter noncoding sequence, despite a 3.1 times higher mutation rate than its adjacent coding N gene, followed a parallel evolutionary pattern.

Amino Acid Sequence↗

PubMed1996

Phylogenetic and epidemiologic analysis of the walleye dermal sarcoma virus.

Walleye dermal sarcoma virus (WDSV) is a newly described retrovirus that is etiologically associated with a multifocal skin tumor of a fish common in North America, the walleye. Tumor prevalence ranges from 27% of adult walleyes in a densely populated lake, Oneida Lake, New York, to 1% in less populated waters. Phylogenetic analysis of the surface (SU) domain of the WDSV envelope gene of isolates from different regions of North America showed that viral isolates formed distinct clusters according to their geographic origin, except viral isolates from Oneida Lake, which were also much more variable. Viral clones isolated from an individual tumor had identical nucleotide sequences. This finding is consistent with tumors developing from single infected dermal cells, and supports the etiological role of this virus in tumor development. Like in other retroviruses, the SU domain of the WDSV env gene was more variable than gag, and the ratio of nonsynonymous over synonymous mutations was comparable to that of the V3 loop of HIV-1. These findings indicate that WDSV SU is the object of strong selective immunologic pressures, like the SU domain of other retroviruses.

Base Sequence↗

PubMed1995

MvaI polymorphism in the proteolipid protein (PLP) gene.

We report a rare polymorphism in the human proteolipid protein (PLP) gene. A synonymous mutation, 168 A-->G, was detected in exon 2 of the PLP gene. Mutations in this gene have been reported in some cases of Pelizaeus-Merzbacher disease.

Base Sequence↗

PubMed1996

Stem-loop potential in MHC genes: a new way of evaluating positive Darwinian selection?

The domains of polymorphic major histocompatibility complex (MHC) proteins which interact with peptides and T-cell receptors are considered to have been under positive evolutionary selection pressure. Evidence for this is a high ratio of non-synonymous to synonymous mutations in the corresponding genomic domains. By this criterion snake venom phospholipase A2 genes have also been under positive selection pressure. Recent studies of the latter genes indicate that positive selection has overridden an evolutionary pressure on base order which normally promotes the potential to extrude single-strand stem-loops from supercoiled duplex DNA ( fold pressure ). This has resulted in base order-dependent stem-loop potential being shifted to introns, which are highly conserved between species. It is now shown that, like snake venom phospholipase A2 genes, the domains of polymorphic MHC genes which appear to have responded to positive selection pressure have decreased base order-dependent stem-loop potential. The evolutionary pressure to generate stem-loop potential (believed to be important for recombination) has been overridden less in exons under negative purifying selection than in exons under positive Darwinian selection. Thus, base order-dependent stem-loop potential shows promise as an independent indicator of positive selection.

Animals↗

PubMed2002

Allelic variation in the squirrel monkey x-linked color vision gene: biogeographical and behavioral correlates.

Most Neotropical primate species possess a polymorphic X-linked and a monomorphic autosomal color vision gene. Consequently, populations are composed of both dichromatics and trichromatics. Most theories on the maintenance of this genetic system revolve around possible advantages for foraging ecology. To examine the issue from a different angle, we compared the numbers and relative frequencies of alleles at the X-linked locus among three species of Saimiri representing a wide range of geographical and behavioral variation in the genus. Exons 3, 4, and 5 of the X-linked opsin gene were sequenced for a large number of X chromosomes for all three species. Several synonymous mutations were detected in exons 4 and 5 for the originally reported alleles but only a single nonsynonymous change was detected. Two alleles were found that appeared to be the result of recombination events. The low occurrence of recombinant alleles and absence of mutations in the amino acids critical for spectral tuning indicates that stabilizing selection acts to maintain the combinations of critical sites specific to each allele. Allele frequencies were approximately the same for all Saimiri species, with a slight but significant difference between S. boliviensis and S. oerstedii. No apparent correlation exists between allele frequencies and behavioral or biogeographical differences between species, casting doubt on the speculation that the spectral sensitivities of the alleles have been maintained because they are specifically well-tuned to Saimiri visual ecology. Rather, the spectral tuning peaks might have been maintained because they are as widely spaced as possible within the limited range of middlewave to longwave spectra useful to all primates. This arrangement creates a balance between maximizing the distance between spectral tuning peaks (allowing the color opponency of the visual system to distinguish between peaks) and maximizing the number of alleles within a limited range (yielding the greatest possible frequency of heterozygotes).

Alleles↗

PubMed2005

Characterization of multiple alleles of the T-cell differentiation marker ART2 (RT6) in inbred and wild rats.

ART2 (RT6) belongs to the family of mono-ADP-ribosyltransferases (ARTs). ART2 is a T-cell differentiation marker expressed by the majority of mature peripheral T cells in the rat. The two known ART2 allotypes display approximately 95% amino acid identity. We sequenced the ART2 coding regions from 18 inbred rat strains and found two additional alleles, termed Art2 ( a2 ) and Art2 ( b2 ). Monoclonal antibody Gy12/61 specifically reacted with Art2 ( a2 ) but not Art2 ( a1 ) lymph node cells. Expression of ART2 allotypes in Jurkat cells confirmed this specificity. A polymerase chain reaction (PCR) assay using restriction fragment length polymorphisms is described, which allows the easy discrimination of Art2 alleles. All four laboratory rat alleles, as well as an additional sequence variant, were found amongst 18 wild rat DNA samples. PCR analysis confirmed the selective presence of a rodent identifier (ID) element in the Art2 ( a ) but not the Art2 ( b ) alleles in all rats studied. Analysis of Art2 ( a1 ) and Art2 ( b2 ) genes showed greater divergence in coding than in non-coding regions. Together with the finding of a high number of non-synonymous mutations leading mostly to non-conservative amino acid substitutions clustered on the side facing away from the cell surface, this suggests that the Art2 polymorphism has been subject to selection.

ADP Ribose Transferases↗

PubMed2006

Nature of allelic sequence polymorphism at the KIR3DL3 locus.

KIR3DL3 is a framework gene of the Leukocyte Receptor Complex, present in all individuals and haplotypes analysed to date. We describe 17 novel KIR3DL3 alleles, including seven single nucleotide polymorphic (SNP) positions within the coding region. Sequence variation within introns included a VNTR within intron 1. As KIR3DL3 mRNA is known to be expressed in decidual NK cells, we investigated the impact of KIR3DL3 allelic variation on pre-eclampsia. No statistical difference in allele frequency or polymorphism was observed between pre-eclampsia patient and control cohorts. Linkage disequilibrium (LD) analysis of exonic SNPs suggested that recombination may be a mechanism of generating sequence diversity within KIR3DL3. A potential recombination hotspot was located within intron 5. A strong LD was detected between polymorphism in exon 6 of KIR3DL3 and the KIR gene -2DL3 or -2DS2 loci, which define the centromeric end of two main haplotypes (A and B) of the KIR cluster. Comparison of primate KIR sequences indicated that the Ig domains of KIR3DL3 are highly conserved between chimpanzee, gorilla and humans. Investigation of KIR3DL3 dN/dS ratios indicated a greater level of synonymous mutations consistent with purifying selection, although positive selection was detected acting on two sites within the stem region.

Alleles↗