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PubMed2005

Mutation screening and association study of the neprilysin gene in sporadic Alzheimer's disease in Chinese persons.

Neprilysin has been reported to be a major beta-amyloid peptide (Abeta)-degrading enzyme. The decreased expression and activity of it may contribute to the development of Alzheimer's disease by promoting the accumulation of Abeta. We used denaturing high-performance liquid chromatography to screen the neprilysin gene (NEP) for single nucleotide polymorphisms (SNPs) in 257 Chinese sporadic Alzheimer's disease patients and 242 cognitive normal controls. As a result, eight novel and one known SNP were identified. Three of them, -204G-->C in the promoter region, IVS17-294C-->T, and IVS22+36C-->A showed a significant association with Alzheimer's disease (p = .006,.017, and.003, respectively). Subsequent haplotype analysis provided further evidence of the association (global p < .0001 for the three SNPs mentioned above, and global p < .01 for the eight SNPs with rare allele frequency > 1%). These findings indicate that genetic variations within or extremely close to NEP might influence the susceptibility to Alzheimer's disease in Chinese persons.

Aged↗

PubMed2006

Polymorphisms in coding and regulatory regions of the porcine MYF6 and MYOG genes and expression of the MYF6 gene in m. longissimus dorsi versus productive traits in pigs.

MYOG and MYF6 belong to the MyoD gene family. They code for the bHLH transcription factors playing a key role in later stages of myogenesis: differentiation and maturation of myotubes. Three SNPs in porcine MYF6 and two in porcine MYOG were analysed in order to establish associations with chosen carcass quality and growth rate traits in Polish Landrace, Polish Large White and line 990 sows. No statistically significant effect of SNP in the promoter region of the MYF6 gene on its expression measured on mRNA level was found. Associations between the genotype at the MYF6 locus and carcass quality traits appeared to be breed-dependent. The C allele in the case of SNP in the promoter region and GC haplotype in exon 1 were advantageous for right carcass side weight in Polish Landrace sows and disadvantageous for this trait in Polish Large White sows. These gene variants were also the most advantageous for loin and ham weight in sows of line 990. The mutation in exon 1 of the MYOG gene had no statistically significant association with carcass quality traits and the mutation in the 3'-flanking region had the breed-dependent effect as well. These results suggest that SNPs analysed in this study are not causative mutations, but can be considered as markers of some other, still unrevealed genetic polymorphism that influences the physiological processes and phenotypic traits considered in this study.

Animals↗

PubMed2005

Complex HTR2C linkage disequilibrium and promoter associations with body mass index and serum leptin.

The occurrence of obesity, eating disorders, and related diseases has increased in many parts of the world. Given that few strong genetic factors have been found, it is clear that these are complex multi-factorial diseases. The serotonin receptor 2C, a member of the 5-HTergic system, has been implicated in the control of phagia and obesity. We report a detailed investigation of linkage disequilibrium (LD) within and between the HTR2C promoter and the flanking sequences around a commonly utilized marker in the second coding exon of HTR2C. We suggest that inconsistent associations between HTR2C and several phenotypes, including obesity, may be due to the LD pattern across the gene in which recombination and gene conversion have been influential. The nucleotide and haplotype distribution is consistent with that of the neutral mutation model. The number of haplotypes suggests demographic influences or over dominant selection that may have a function in HTR2C expression. Using the fine LD pattern, we describe a possible association with promoter haplotypes and diplotypes, including a GT microsatellite, and body mass index (BMI) > or =30 kgm(-2) (P<0.0001). SNP -995G>A heterozygotes, as well as promoter diplotypes, were found to marginally influence higher serum leptin corrected for percentage body fat (P=0.01), which might suggest that these subjects are leptin resistant. Our results complement previous studies of HTR2C in both mice and humans, and suggest the importance of genetic variation and elucidating the fine LD structure in uncovering the genetic factors of obesity.

Adult↗

PubMed2005

Phenotype severity and genetic variation at the disease locus: an investigation of nail dysplasia in the nail patella syndrome.

The genetic bases underlying the range and severity of phenotypes in Mendelian disorders is poorly understood; however, improvements in this area have the potential to facilitate analysis of oligogenic disorders. The nail dysplasia observed in Nail Patella Syndrome (NPS) was selected as a quantifiable variable within a Mendelian disorder, for which data could be readily obtained, to allow investigation of the genetic basis of variation. Analysis of SNP haplotypes across the LMX1B gene demonstrated association between the haplotype of the mutant allele and the variability in the nail score (p = 0.024). These results are in contrast to those obtained previously, which supported a modifying role for the wild-type allele. Since there is no evidence that particular mutations, or classes of mutation, are associated with the variation (p > 0.5), further work is required to identify the elements associated with the LMX1B gene that mediate phenotypic severity.

DNA Mutational Analysis↗

PubMed2000

Precise estimation of allele frequencies of single-nucleotide polymorphisms by a quantitative SSCP analysis of pooled DNA.

We show that single-nucleotide polymorphisms (SNPs) of moderate to high heterozygosity (minor allele frequencies >10%) can be efficiently detected, and their allele frequencies accurately estimated, by pooling the DNA samples and applying a capillary-based SSCP analysis. In this method, alleles are separated into peaks, and their frequencies can be reliably and accurately quantified from their peak heights (SD <1.8%). We found that as many as 40% of publicly available SNPs that were analyzed by this method have widely differing allele frequency distributions among groups of different ethnicity (parents of Centre d'Etude Polymorphisme Humaine families vs. Japanese individuals). These results demonstrate the effectiveness of the present pooling method in the reevaluation of candidate SNPs that have been collected by examination of limited numbers of individuals. The method should also serve as a robust quantitative technique for studies in which a precise estimate of SNP allele frequencies is essential-for example, in linkage disequilibrium analysis.

Alleles↗

PubMed2006

Variant of the CHEK2 gene as a prognostic marker in glioblastoma multiforme.

OBJECTIVE: Germline mutations of the CHEK2 tumor suppressor gene have been found in families with the Li-Fraumeni syndrome (LFS). Patients with LFS experience a variety of cancers, including malignant astrocytomas. We investigated a potential role for a CHEK2 gene polymorphism in glioblastomas. METHODS: A genetic polymorphism of the CHEK2 gene (CHEK2 SNP rs2017309 A/T) was genotyped in a series of glioblastoma patients (n = 213) and population controls (n = 192). Subsets of tumors were analyzed for loss of heterozygosity 22q(n = 66), loss of heterozygosity CHEK2 (n = 53), CHEK2 expression (n = 21), and CHEK2 coding sequence alterations (n = 18). CHEK2 SNP rs2017309 genotyping findings and traditional clinicopathological parameters were correlated with the patients' prognoses. RESULTS: No association between the CHEK2 SNP and glioblastoma formation was observed. No CHEK2 coding sequence aberrations or tumors completely lacking CHEK2 protein were identified. However, the presence of the CHEK2 rs2017309 A allele was significantly associated with an adverse prognosis (P = 0.034), particularly among patients undergoing postoperative chemotherapy and radiotherapy (n = 28, median survival 10.5 versus 15.5 mo, P = 0.008). We could confirm the patients' age, Karnofsky Performance Scale score, and postoperative radiotherapy and chemotherapy (all P < 0.0001, log-rank test) as decisive prognostic factors. CONCLUSION: Our data suggest that a CHEK2 gene polymorphism might correlate with the prognosis of glioblastoma patients. These findings may point to an as yet unrecognized role for the CHEK2 gene in glioblastomas.

Biomarkers↗

PubMed2002

New generation pharmacogenomic tools: a SNP linkage disequilibrium Map, validated SNP assay resource, and high-throughput instrumentation system for large-scale genetic studies.

Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies--specifically for candidate-gene, candidate-region, and whole-genome association studies--will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics' human genome assembly and enormous resource ofphysically mapped SNPs (approximately 4,000,000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency ofthe polymorphisms. We also discuss an advanced, high-performance SNP assay chemisty--a new generation of the TaqMan probe-based, 5' nuclease assay-and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.

Alleles↗

PubMed2005

ETHE1 mutations are specific to ethylmalonic encephalopathy.

Mutations in ETHE1, a gene located at chromosome 19q13, have recently been identified in patients affected by ethylmalonic encephalopathy (EE). EE is a devastating infantile metabolic disorder, characterised by widespread lesions in the brain, hyperlactic acidaemia, petechiae, orthostatic acrocyanosis, and high levels of ethylmalonic acid in body fluids. To investigate to what extent ETHE1 is responsible for EE, we analysed this gene in 29 patients with typical EE and in 11 patients presenting with early onset progressive encephalopathy with ethylmalonic aciduria (non-EE EMA). Frameshift, stop, splice site, and missense mutations of ETHE1 were detected in all the typical EE patients analysed. Western blot analysis of the ETHE1 protein indicated that some of the missense mutations are associated with the presence of the protein, suggesting that the corresponding wild type amino acid residues have a catalytic function. No ETHE1 mutations were identified in non-EE EMA patients. Experiments based on two dimensional blue native electrophoresis indicated that ETHE1 protein works as a supramolecular, presumably homodimeric, complex, and a three dimensional model of the protein suggests that it is likely to be a mitochondrial matrix thioesterase acting on a still unknown substrate. Finally, the 625G-->A single nucleotide polymorphism in the gene encoding the short chain acyl-coenzyme A dehydrogenase (SCAD) was previously proposed as a co-factor in the aetiology of EE and other EMA syndromes. SNP analysis in our patients ruled out a pathogenic role of SCAD variants in EE, but did show a highly significant prevalence of the 625A alleles in non-EE EMA patients.

Alleles↗

PubMed2001

Polymorphisms in PNLIP, encoding pancreatic lipase, and associations with metabolic traits.

Pancreatic lipase (EC 3.1.1.3) is an exocrine secretion that hydrolyzes dietary triglycerides in the small intestine. We developed genomic amplification primers to sequence the 13 exons of PNLIP, which encodes pancreatic lipase, in order to screen for possible mutations in cell lines of four children with pancreatic lipase deficiency (OMIM 246600). We found no missense or nonsense mutations in these samples, but we found three silent single-nucleotide polymorphisms (SNPs), namely, 96A/C in exon 3, 486C/T in exon 6, and 1359C/T in exon 13. In 50 normolipidemic Caucasians, the PNLIP 96C and 486T alleles had frequencies of 0.083 and 0.150, respectively. The PNLIP 1359T allele was absent from Caucasian, Chinese, South Asian, and North American aboriginal samples, but had a frequency of 0.085 in an African sample, suggesting that it is a population-specific variant. In an association analysis of 185 African neonates, the PNLIP 1359C/T SNP genotype was significantly associated with concentrations of plasma lipoproteins. These associations were most likely due to linkage disequilibrium with another functional variant at or near PNLIP. Thus, we report three new SNPs for the PNLIP, which may serve as markers for association analyses and for pharmacogenetic studies of pancreatic lipase inhibitors.

Africa↗

PubMed2005

Polymorphisms in DNA repair genes and epithelial ovarian cancer risk.

DNA repair gene polymorphisms and mutations are known to influence cancer risk. We studied whether polymorphisms in DNA double strand break (DSB) repair genes are associated with epithelial ovarian cancer (EOC) risk. Up to 1,600 cases and 4,241 controls from 4 separate genetic association studies from 3 countries were genotyped for 13 single nucleotide polymorphisms (SNP) in 6 genes (BRCA1, NBS1, RAD51, RAD52, XRCC2 and XRCC3) involved in homologous recombination of DNA double strand breaks. Genotype specific risks were estimated as odds ratios (OR) by unconditional logistic regression. No association was detected between EOC risk and BRCA1 Q356R, BRCA1 P871L, RAD51 g135c, RAD51 g172t, RAD52 c2259t, NBS1 L34L, NBS1 E185Q, NBS1 A399A, NBS1 P672P, XRCC2 g4324c, XRCC2 c41657t and XRCC3 T241M. The XRCC2 R188H polymorphism was associated with a modest reduction in EOC risk: OR for heterozygotes was 0.8 (95% confidence interval [CI] = 0.7-1.0) and for rare homozygotes 0.3 (0.1-0.9). The XRCC3 a4541g polymorphism, situated in the 5'UTR, and the intronic XRCC3 a17893g polymorphism were not associated with EOC risk in general, but when the serous EOC subset only was analysed, the OR for heterozygotes for a4541g was 1.0 (0.9-1.2) and for the rare homozygotes 0.5 (0.3-0.9). For the XRCC3 a17893g polymorphism, the OR for the heterozygotes and the rare homozygotes were 0.8 (0.7-0.9) and 0.9 (0.7-1.2), respectively. In our study, some polymorphisms in XRCC2 and XRCC3 genes were associated with EOC risk. Further research on the role of these genes on epithelial ovarian cancer is warranted.

Adult↗

PubMed2003

Lrmp and Bcat1 are candidates for the type I diabetes susceptibility locus Idd6.

Three type 1 diabetes associated regions on distal mouse chromosome 6 have recently been defined by the construction and analysis of a series of congenic strains, carrying C3H/HeJ genomic material on a NOD/Lt genetic background. Whilst NOD/Lt alleles at the most distal locus Idd6 confer susceptibility, C3H/HeJ alleles confer resistance to diabetes. Idd6 overlaps with a locus controlling low rates of proliferation in immature NOD-thymocytes, suggesting that Idd6 could be controlling diabetes development through an effect on T cell proliferation rates. Candidates for Idd6 therefore include genes, which are implicated in the immune system and/or in the control of cell proliferation rates, such as Lrmp (Jaw1), Bcat1 and Kras2 that map to the Idd6 candidate region. In the present study, we have undertaken an expression and mutational analysis of all three genes. A surprisingly large number of polymorphisms and amino acid changes were identified in both Lrmp and Bcat1 indicating that they are candidates for Idd6. The two genes are located within a genomic interval of about 3 Mb that contains a large number of single nucleotide polymorphisms (SNP) and which has possibly been derived from distinct ancestral haplotypes in the C3H/HeJ and NOD/Lt strains.

Animals↗

PubMed2006

A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses.

Fasting glucose is associated with future risk of type 2 diabetes and ischemic heart disease and is tightly regulated despite considerable variation in quantity, type, and timing of food intake. In pregnancy, maternal fasting glucose concentration is an important determinant of offspring birth weight. The key determinant of fasting glucose is the enzyme glucokinase (GCK). Rare mutations of GCK cause fasting hyperglycemia and alter birth weight. The extent to which common variation of GCK explains normal variation of fasting glucose and birth weight is not known. We aimed to comprehensively define the role of variation of GCK in determination of fasting glucose and birth weight, using a tagging SNP (tSNP) approach and studying 19,806 subjects from six population-based studies. Using 22 tSNPs, we showed that the variant rs1799884 is associated with fasting glucose at all ages in the normal population and exceeded genomewide levels of significance (P=10-9). rs3757840 was also highly significantly associated with fasting glucose (P=8x10-7), but haplotype analysis revealed that this is explained by linkage disequilibrium (r2=0.2) with rs1799884. A maternal A allele at rs1799884 was associated with a 32-g (95% confidence interval 11-53 g) increase in offspring birth weight (P=.002). Genetic variation influencing birth weight may have conferred a selective advantage in human populations. We performed extensive population-genetics analyses to look for evidence of recent positive natural selection on patterns of GCK variation. However, we found no strong signature of positive selection. In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth.

Adult↗

PubMed2006

Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex changes and multiple forms of chromosomal instability in colorectal cancers.

Cancers with chromosomal instability (CIN) are held to be aneuploid/polyploid with multiple large-scale gains/deletions, but the processes underlying CIN are unclear and different types of CIN might exist. We investigated colorectal cancer cell lines using array-comparative genomic hybridization (CGH) for copy number changes and single-copy number polymorphism (SNP) microarrays for allelic loss (LOH). Many array-based CGH changes were not found by LOH because they did not cause true reduction-to-homozygosity. Conversely, many regions of SNP-LOH occurred in the absence of copy number change, comprising an average per cell line of 2 chromosomes with complete LOH; 1-2 terminal regions of LOH (mitotic recombination); and 1 interstitial region of LOH. SNP-LOH detected many novel changes, representing possible locations of uncharacterized tumor suppressor loci. Microsatellite unstable (MSI+) lines infrequently showed gains/deletions or whole-chromosome LOH, but their near-diploid karyotypes concealed mitotic recombination frequencies similar to those of MSI- lines. We analyzed p53 and chromosome 18q (SMAD4) in detail, including mutation screening. Almost all MSI- lines showed LOH and/or deletion of p53 and 18q; some near-triploid lines had acquired three independent changes at these loci. We found consistent results in primary colorectal cancers. Overall, the distributions of mitotic recombination and whole-chromosome LOH in the MSI- cell lines differed significantly from random, with some lines having much higher than expected levels of these changes. Moreover, lines with more LOH changes had significantly fewer copy number changes. These data suggest that CIN is not synonymous with copy number change and some cancers have a specific tendency to whole-chromosome deletion and regain or to mitotic recombination.

Cell Line, Tumor↗

PubMed2001

A semi-automated system for analysis and storage of SNPs.

The discovery of single nucleotide polymorphisms ( SNPs) is currently pursued with a tremendous effort. SNPs represent a rich source for molecular markers, since estimations predict six to seven million of these DNA variations in the human genome. A subset of these genetic variants is thought to have a pervasive impact on modern medicine, be it for the elucidation of differential pharmacological response or for the facilitated identification of genes involved in monogenetic and complex human diseases. Here we describe the overall process that leads to the set up of a SNP database. We describe a high-throughput sequencing assay for SNP discovery, automation of the dataflow from the DNA sequencer to the SNP analysis, and the tools to facilitate it. At the end of the process, a web-accessible interface collects the SNP information, which is processed in order to be written into the SNP database and to be available for end users who would like to select appropriate SNPs for their special screening needs.

Automation↗

PubMed2006

SNP Function Portal: a web database for exploring the function implication of SNP alleles.

MOTIVATION: Finding the potential functional significance of SNPs is a major bottleneck in understanding genome-wide SNP scanning results, as the related functional data are distributed across many different databases. The SNP Function Portal is designed to be a clearing house for all public domain SNP functional annotation data, as well as in-house functional annotations derived from different data sources. It currently contains SNP functional annotations in six major categories including genomic elements, transcription regulation, protein function, pathway, disease and population genetics. Besides extensive SNP functional annotations, the SNP Function Portal includes a powerful search engine that accepts different types of genetic markers as input and identifies all genetically related SNPs based on the HapMap Phase II data as well as the relationship of different markers to known genes. As a result, our system allows users to identify the potential biological impact of genetic markers and complex relationships among genetic markers and genes, and it greatly facilitates knowledge discovery in genome-wide SNP scanning experiments. AVAILABILITY: http://brainarray.mbni.med.umich.edu/Brainarray/Database/SearchSNP/snpfunc.aspx.

Alleles↗

PubMed2007

Lack of evidence of an allelic association of a functional GABRB3 exon 1a promoter polymorphism with idiopathic generalized epilepsy.

PURPOSE: Mutation screening and linkage disequilibrium mapping of the gene encoding the GABA(A) beta(3) subunit (GABRB3) identified a common genetic variant in the exon 1a promoter region (C-allele of rs4906902) which displayed a reduced transcriptional activity and showed a strong allelic association with childhood absence epilepsy (CAE). The present population-based association study tested whether the C-allele of rs4906902 confers susceptibility to CAE or other common syndromes of idiopathic generalized epilepsy (IGE) in a German sample. METHODS: Seven hundred and eighty unrelated German IGE patients (250 CAE, 123 juvenile absence epilepsy, 303 juvenile myoclonic epilepsy (JME), 104 epilepsy with generalized tonic-clonic seizures on awakening) and 559 healthy population controls were genotyped for the single nucleotide polymorphism (SNP) rs4906902. RESULTS: The frequency of the risk-conferring C-allele did not differ significantly between CAE patients (f(C)=0.190) and controls (f(C)=0.183; P=0.376, one-tailed). Similarly, no evidence for an allelic association was found for 373 patients with idiopathic absence epilepsy, 303 JME patients, and the entire IGE sample (P>0.77, two-tailed). CONCLUSION: Our study failed to replicate an association of the common GABRB3 exon 1a promoter SNP rs4906902 with CAE. Moreover, the present results do not provide evidence that the common functional C-variant confers a substantial epileptogenic effect to a broad spectrum of IGE syndromes in the German population.

Alleles↗

PubMed2004

Susceptibility to Paget's disease of bone is influenced by a common polymorphic variant of osteoprotegerin.

UNLABELLED: To clarify the role of the TNFRSF11B gene encoding osteoprotegerin (OPG), in Paget's disease of bone (PDB) we studied TNFRSF11B polymorphisms in an association study of 690 UK subjects and in a worldwide familial study of 66 kindreds. We found that the G1181 allele of TNFRSF11B, encoding lysine at codon 3 of the OPG protein, predisposes to both sporadic and familial PDB. INTRODUCTION: Paget's disease of bone (PDB) is a common disorder characterized by focal abnormalities of bone turnover. Genetic factors are important in the pathogenesis of PDB, and studies have shown that inactivating mutations of the TNFRSF11B gene, encoding osteoprotegerin (OPG), cause the rare syndrome of juvenile Paget's disease. In this study, we sought to determine whether polymorphisms of the TNFRSF11B gene contribute to the pathogenesis of classical PDB. MATERIALS AND METHODS: We screened for polymorphisms of the TNFRSF11B gene by DNA sequencing of the proximal promoter, coding exons, and intron-exon boundaries in 20 PDB patients and 10 controls. Informative single nucleotide polymorphisms (SNPs), including a G1181C SNP, which predicts a lysine-asparagine substitution at codon 3 of the OPG signal peptide and haplotypes, were related to the presence of PDB in 312 cases compared with 378 controls and to transmission of PDB in 140 affected offspring from 66 kindreds with familial PDB. RESULTS AND CONCLUSIONS: The G1181 allele was significantly over-represented in PDB patients (chi(2) = 5.7, df = 1, p = 0.017, adjusted alpha = 0.024), equivalent to an odds ratio for PDB of 1.55 (95% CI: 1.11-2.16). The distribution of TNFRSF11B haplotypes significantly differed in sporadic PDB cases and controls (chi(2) = 30.2, df = 9, p < 0.001) because of over-representation of haplotypes containing the G1181 allele in cases. The family study showed that the most common haplotype containing the G1181 allele was transmitted more frequently than expected to 140 individuals with familial PDB (chi(2) = 7.35, df = 1, p < 0.01), and the transmission disequilibrium was even more pronounced in a subgroup of 78 familial PDB patients who did not carry mutations of the SQSTM1 gene (chi(2) = 8.44, df = 1, p < 0.005). We conclude that the G1181 allele of TNFRSF11B, encoding lysine at codon 3 of the OPG protein, predisposes to the development of sporadic PDB and familial PDB that is not caused by SQSTM1 mutations.

Aged↗

PubMed2006

Single-nucleotide polymorphisms in porcine mannan-binding lectin A.

The MBL1 and MBL2 genes encode mannan-binding lectins (MBL) A and C, respectively, that are collagenous lectins (collectins) produced mainly by the liver. Several single-nucleotide polymorphisms (SNPs) in the human MBL2 gene are responsible for various innate immune dysfunctions due to abnormal structure or expression of human MBL-C. The MBL1 gene encodes MBL-A, which has bacteria-binding properties in pigs and rodents but is mutated to a pseudogene in humans and chimpanzees. In these studies, we surveyed both porcine MBL genes for SNPs that might impair disease resistance. Single-strand conformational polymorphism (SSCP) analysis of MBL cDNAs from porcine liver revealed three SNPs within the coding region of MBL1 in various breeds of pigs. One nonsynonymous SNP that substituted cysteine for glycine in the collagen-like domain of pig MBL-A was found by a multiplex PCR test in all European pig breeds examined, with allele frequencies ranging from 1.4 to 46.4%. No SNPs were identified in the coding region of porcine MBL2 but the expression of MBL-C in the liver was widely variable in comparison to the expression of MBL-A, GAPDH, PigMAP, and haptoglobin. These results indicate that some pigs have a miscoding defect in MBL-A and a possible expression defect in MBL-C, which are analogous to coding and promoter polymorphisms that affect human MBL-C.

Amino Acid Sequence↗