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Results for “nucleotide polymorphism patterns”

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PubMed1993

Unidirectional dominance of cytoplasmic inheritance in two genetic crosses of Plasmodium falciparum.

Malarial parasites have two highly conserved cytoplasmic DNA molecules: a 6-kb tandemly arrayed DNA that has characteristics of a mitochondrial genome, and a 35-kb circular DNA that encodes functions commonly found in chloroplasts. We examined the inheritance pattern of these elements in two genetic crosses of Plasmodium falciparum clones. Parent-specific oligonucleotide probes and single-strand conformation polymorphism analysis identified single nucleotide changes that distinguished the parental 6- and 35-kb DNA molecules in the progeny. In all 16 independent recombinant progeny of a cross between a Central American clone, HB3, and a Southeast Asian clone, Dd2, the 6- and 35-kb DNAs were inherited from the Dd2 parent. In all nine independent recombinant progeny of a cross between clone HB3 and a likely African clone, 3D7, the 6-kb DNA was inherited from the 3D7 parent. Inheritance of cytoplasmic genomes of the Dd2 and 3D7 parents was, therefore, dominant over that of the HB3 parent. Cytoplasmic DNA molecules were found almost exclusively in the female gametes of malarial parasites; hence, clone HB3 did not appear to have served as a maternal parent for the progeny of two crosses. Defective differentiation into male gametes by clone Dd2 is likely to be a reason for the cytoplasmic inheritance pattern seen in the HB3 x Dd2 cross. However, incompetence of male or female gametes is unlikely to explain the uniparental dominance in recombinant progeny of the HB3 x 3D7 cross, since both parents readily self-fertilized and completed the malaria life cycle on their own. Instead, the data suggest unidirectional parental incompatibility in cross-fertilization of these malarial parasites, where a usually cosexual parental clone can participate only as a male or as a female. Such an incompatibility may be speculated as indicating an early phase of reproductive isolation of P. falciparum clones from different geographical regions.

Animals↗

PubMed2000

Overexpression of the hOGG1 gene and high 8-hydroxy-2'-deoxyguanosine (8-OHdG) lyase activity in human colorectal carcinoma: regulation mechanism of the 8-OHdG level in DNA.

8-Hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most abundant oxidatively modified lesions in DNA. Our previous study (Kondo et al, Free Radic. Biol. Med., 27: 401-410, 1999) revealed that human colorectal carcinoma cells are oxidatively stressed based on 8-OHdG determination. To elucidate 8-OHdG metabolism and its clinical significance in colorectal carcinoma, we studied the 8-OHdG repair system in DNA by measuring specific lyase activity and hOGG1 expression using quantitative-competitive reverse transcription-PCR. In addition, we searched for the presence of mutations and single nucleotide polymorphisms of the hOGG1 gene by single-strand conformational polymorphism and sequencing analyses. It was found that 8-OHdG-specific lyase activity and hOGG1 expression were significantly up-regulated in carcinoma, and a proportional association between 8-OHdG levels and either 8-OHdG lyase activity (r = 0.641, P < 0.05) or hOGG1 expression (r = 0.702, P < 0.05) was present. Whereas no difference was detected in the 8-OHdG level between early- and advanced-stage cancer, lyase activity (1.2-fold) and hOG1 expression (1.6-fold) were significantly increased in advanced-stage cancer. No mutation was found in the 25 tumors examined. Three kinds of single nucleotide polymor. phism were observed, including that of codon 326 (Ser/Cys) in exon 7. However, there was no correlation between any of the three polymorphic patterns and either 8-OHdG level or lyase activity. These results suggest that increased 8-OHdG levels in colorectal carcinoma are attributed to increased formation and are maintained by induced 8-OHdG repair activity at appropriate high levels. Our results may offer a unique approach in the development of preventive and therapeutic interventions as well as new insights into the pathogenesis of colorectal carcinoma.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1993

The random amplification of polymorphic DNA allows the identification of strains and species of schistosome.

The use of arbitrarily selected primers (10-24 nucleotides) and very low stringency annealing conditions (30 degrees C followed by 40 degrees C) for the polymerase chain reaction amplification of 1.0 ng of schistosome DNA resulted in relatively complex patterns of products. Amongst the primers tested some, for example 5'-TCGTAGCCAA, produced patterns that included bands that were polymorphic between strains of Schistosoma mansoni. Other primers, for example 5'-TCACGATGCA, produced apparently identical products using DNA from 5 S. mansoni strains but highly variable patterns when DNA from different schistosome species was used. The results indicate that the random amplification of polymorphic DNA (RAPD) may be an extremely useful approach to the identification of schistosome strains and species.

Animals↗

PubMed2000

Survey of the fragile X syndrome CGG repeat and the short-tandem-repeat and single-nucleotide-polymorphism haplotypes in an African American population.

Previous studies have shown that specific short-tandem-repeat (STR) and single-nucleotide-polymorphism (SNP)-based haplotypes within and among unaffected and fragile X white populations are found to be associated with specific CGG-repeat patterns. It has been hypothesized that these associations result from different mutational mechanisms, possibly influenced by the CGG structure and/or cis-acting factors. Alternatively, haplotype associations may result from the long mutational history of increasing instability. To understand the basis of the mutational process, we examined the CGG-repeat size, three flanking STR markers (DXS548-FRAXAC1-FRAXAC2), and one SNP (ATL1) spanning 150 kb around the CGG repeat in unaffected (n=637) and fragile X (n=63) African American populations and compared them with unaffected (n=721) and fragile X (n=102) white populations. Several important differences were found between the two ethnic groups. First, in contrast to that seen in the white population, no associations were observed among the African American intermediate or "predisposed" alleles (41-60 repeats). Second, two previously undescribed haplotypes accounted for the majority of the African American fragile X population. Third, a putative "protective" haplotype was not found among African Americans, whereas it was found among whites. Fourth, in contrast to that seen in whites, the SNP ATL1 was in linkage equilibrium among African Americans, and it did not add new information to the STR haplotypes. These data indicate that the STR- and SNP-based haplotype associations identified in whites probably reflect the mutational history of the expansion, rather than a mutational mechanism or pathway.

Black or African American↗

PubMed2026

Shared genetic architecture and therapeutic targets across paediatric immune-mediated diseases.

OBJECTIVES: Paediatric-onset immune-mediated inflammatory diseases (IMIDs), including juvenile idiopathic arthritis and related rheumatic diseases, remain genetically undercharacterised. We aimed to define shared and category-specific genetic architecture across paediatric IMIDs, compare signals with adult IMIDs, and identify therapeutic opportunities. METHODS: We analysed 24 paediatric IMIDs classified as autoimmune, polygenic-autoinflammatory, mixed-pattern, or allergic. Genome-wide association analyses included 18,086 cases and 131,019 controls of European ancestry. We estimated single nucleotide polymorphism (SNP)-based heritability, genetic correlations, and polygenic overlap; performed subset-based meta-analysis; and conducted functional annotation, gene prioritisation, pathway and protein network analyses, adult-IMID comparison, and drug-target prioritisation. RESULTS: SNP-based heritability ranged from 28.9% for allergic IMIDs to 61.9% for autoimmune IMIDs. Genetic correlation and polygenic modelling supported partial sharing across categories with category-specific components. Meta-analysis identified 39 genome-wide significant loci outside the Major Histocompatibility Complex (MHC) region, including 15 previously unreported loci; 19 loci were shared between categories. Gene-prioritisation and protein interaction analyses identified a core MHC-centred antigen-presentation network, with category-enriched modules involving complement, innate/barrier pathways, epithelial biology, and type 2 immunity. Enriched pathways included nuclear factor κB signalling, T helper 17 related pathways, Janus kinase-signal transducer and activator of transcription signalling, programmed cell death protein 1/programmed death‑ligand 1, cytotoxic T‑lymphocyte associated protein 4 regulation, and osteoclast differentiation, several of which are relevant to rheumatic diseases. Paediatric IMIDs shared broad polygenic architecture with adult IMIDs, whereas top-ranked genes converged strongly with adult rheumatic diseases. Priority Index analysis identified 178 high-scoring genes, including 43 approved or investigational IMID drug targets. CONCLUSIONS: Paediatric-onset IMIDs share core pathways with adult forms but exhibit distinct genetic architecture shaped by age-specific immune and neurodevelopmental biology. These findings provide a genomic framework for paediatric precision medicine, guiding classification, risk prediction, and therapeutic development.

Humans↗

PubMed2000

Cladistic structure within the human Lipoprotein lipase gene and its implications for phenotypic association studies.

Haplotype variation in 9.7 kb of genomic DNA sequence from the human lipoprotein lipase (LPL) gene was scored in three populations: African-Americans from Jackson, Mississippi (24 individuals), Finns from North Karelia, Finland (24), and non-Hispanic whites from Rochester, Minnesota (23). Earlier analyses had indicated that recombination was common but concentrated into a hotspot and that recurrent mutations at multiple sites may have occurred. We show that much evolutionary structure exists in the haplotype variation on either side of the recombinational hotspot. By peeling off significant recombination events from a tree estimated under the null hypothesis of no recombination, we also reveal some cladistic structure not disrupted by recombination during the time to coalescence of this variation. Additional cladistic structure is estimated to have emerged after recombination. Many apparent multiple mutational events at sites still remain after removing the effects of the detected recombination/gene conversion events. These apparent multiple events are found primarily at sites identified as highly mutable by previous studies, strengthening the conclusion that they are true multiple events. This analysis portrays the complexity of the interplay among many recombinational and mutational events that would be needed to explain the patterns of haplotype diversity in this gene. The cladistic structure in this region is used to identify four to six single-nucleotide polymorphisms (SNPs) that would provide disequilibrium coverage over much of this region. These sites may be useful in identifying phenotypic associations with variable sites in this gene. Evolutionary considerations also imply that the SNPs in the 3' region should have general utility in most human populations, but the 5' SNPs may be more population specific. Choosing SNPs at random would generally not provide adequate disequilibrium coverage of the sequenced region.

Black or African American↗

PubMed2000

[Detection of core promoter mutations in chronic hepatitis B].

OBJECTIVE: To study the core promoter mutation in chronic hepatitis B and its effect on viral serology. METHODS: HBV core promoter gene fragments were amplified by using mismatched PCR combined with a restriction fragment length polymorphism assay. The PCR products were digested with Bcl I and subjected to electrophoresis on agarose gels. RESULTS: We investigated the core promoter mutation in 89 patients with HBV DNA positive. The patterns of restriction fragment length polymorphism (RFIP) of the core promoter gene were distinguished and verified by direct sequencing. The combined mutations of nucleotides (nt) 1762 and 1764 in the core promoter from A to T and G to A were detected in 47 individuals, 21 of 43 HBeAg positive patients and 26 of 46 anti- HBe positive cases were found infected with this combined mutant. These two groups showed no significant difference (P > 0.05). The combined mutation was found in 11 of the 15 patients with medium and severe chronic hepatitis. In 5 chronic hepatitis B patients with coexistence of wild-type and mutant a tendency of superior accumulation of mutant was found. CONCLUSIONS: This study suggests that the core promoter mutations commonly exist in Chinese chronic hepatitis B patients. The mutation can only reduce the pre-core mRNA transcribing efficiency, but cannot discontinue the synthesis of HBeAg. The effect on serology in this mutation is different from that in pre-core stop 28 mutation. The superior accumulation of mutations seems relating to the degree of chronic liver disease.

Adolescent↗

PubMed1999

Characterisation of the lpdA gene from Neisseria meningitidis by polymerase chain reaction, restriction fragment length polymorphism and sequencing.

P64k protein from Neisseria meningitidis is well recognised in sera from individuals convalescent from meningococcal disease or vaccinated with the Cuban antimeningococcal vaccine VA-MENGOC-BC. The presence of the protein in more than 80 meningococcal strains has also been verified. It is immunogenic in animal models and the antibodies elicited show bactericidal activity against meningococci. To further investigate at the molecular level whether lpdA, the gene coding for P64k protein, is conserved among different N. meningitidis strains, a total of 20 strains isolated from different geographic areas were differentiated on the basis of restriction fragment length polymorphism (RFLP) patterns after polymerase chain reaction (PCR) amplification of the lpdA gene and restriction endonuclease digestion with HpaII. Although a total of five different PCR-RFLP patterns were present, nucleotide sequence determination showed that identity levels were as high as 93-99% among the N. meningitidis strains analysed.

Amino Acid Sequence↗

PubMed1998

Definition and distribution analysis of glycoprotein B gene alleles of human herpesvirus 7.

As for other herpesviruses, glycoprotein B (gB) of human herpesvirus 7 (HHV-7) is believed to play a major role in virus infection and as a target of the host immunogenic response. Using nested PCR, we amplified the whole HHV-7 gB gene from 108 human peripheral blood mononuclear cell samples and studied its variability. By means of restriction fragment length polymorphism (RFLP) analysis, three distinct patterns, designated I, II, and III, were defined and detected at frequencies of 93, 5, and 2%, respectively. Determination of the nucleotide sequence allowed us to recognize five critical positions in the gB gene with six specific combinations of point changes at these positions. These combinations were gB alleles A, B, C, D, E, and F. Alleles D and E corresponded to RFLP patterns II and III, respectively, while the other four alleles corresponded to RFLP pattern I. Identical gB alleles were detected in serial samples as well as in paired samples of blood and saliva from the same individuals, except for one case. In contrast, the distribution of gB alleles differed according to the geographical origin of the human samples: C was the most frequent allele in both African and Caribbean samples, whereas F was the most frequent allele in European ones. Although none of the allele-specific nucleotide changes induced any modification at the protein level, the definition of gB alleles provided convenient viral markers for the study of both HHV-7 infections and human population genetics.

Africa↗

PubMed2001

Nucleotide polymorphism and natural selection at the pantophysin (Pan I) locus in the Atlantic cod, Gadus morhua (L.).

Molecular studies of nucleotide sequence variation have rarely attempted to test hypotheses related to geographically varying patterns of natural selection. The present study tested the role of spatially varying selection in producing significant linkage disequilibrium and large differences in the frequencies of two common alleles at the pantophysin (Pan I) locus among five populations of the Atlantic cod, Gadus morhua. Nucleotide sequences of 124 Pan I alleles showed strong evidence for an unusual mix of balancing and directional selection but no evidence of stable geographically varying selection. The alleles were highly divergent at both the nucleotide level (differing on average by 19 mutations) and at amino acid level (each having experienced three amino acid substitutions since diverging from a common ancestral allele). All six amino acid substitutions occurred in a 56-residue intravesicular loop (IV1 domain) of the vesicle protein and each involved a radical change. An analysis of molecular variation revealed significant heterogeneity in the frequencies of recently derived mutations segregating within both allelic classes, suggesting that two selective sweeps may be presently occurring among populations. The dynamic nature of the Pan I polymorphism in G. morhua and clear departure from equilibrium conditions invalidate a simple model of spatially varying selection.

Alleles↗

PubMed1995

Genotyping of ABO blood groups by PCR and RFLP analysis of 5 nucleotide positions.

The genotyping of ABO blood groups was performed using the polymerase chain reaction (PCR) method. The 4 DNA fragments containing the nucleotide position 261, 526, 703 and 796 of cDNA from A-transferase were amplified by PCR, and the amplified DNA subjected to restriction fragment length polymorphism (RFLP) analysis. The different nucleotide at position 803 was clearly distinguished by electrophoresis of the PCR products amplified with allele-specific primers. By analyzing the electrophoresis patterns, ABO genotyping was conclusively accomplished. The frequencies of ABO genotypes found in Japanese blood donors with A and B phenotypes were as follows: in the phenotype A group, AA = 19.8% and AO = 80.2%; and in the phenotype B group, BB = 12.8% and BO = 87.2%.

ABO Blood-Group System↗

PubMed1991

Genetic variation of putative core gene in hepatitis C virus.

Genetic variation of hepatitis C virus was assessed. We prepared RNA fractions from 21 patients' sera which were positive for hepatitis C virus RNA, synthesized their cDNAs, and amplified fragments, 406 base pairs, encoding a putative core protein, by polymerase chain reaction. One of them, N 15, was cloned and sequenced. N 15 showed 92.4% homology at the nucleotide level and 97.0% homology at the amino acid level compared with HC-J 1 which is the first isolated clone in Japan and similar to that isolated in USA. By restriction fragment length polymorphisms analysis, 14 out of 21 patients (66.7%) showed the same pattern as N 15. No patients showed the pattern of HC-J 1. We could not find a correlation between the genetic variation and clinical features of hepatitis C virus infection. These results indicate that the region, which encodes the core protein and is believed to be relatively conserved in hepatitis C virus genome, has several variations at the nucleotide level, and the major part of hepatitis C virus in Okayama district is different from HC-J 1 and the USA clone.

Adult↗

PubMed2000

The impact of genomics on therapeutic drug development.

Genomics can be defined as a set of related technologies that are focused on the discovery of genes implicated in human disease. Although many of the estimated 100,000 genes in the human genome have been at least partially identified by nucleotide sequence, elucidation of biological function has been achieved for only a small percentage of these. An even smaller percentage of genes discovered by these methodologies have become valid drug targets. This review discusses the various genomics technologies and their likelihood of yielding therapeutic drugs. Emerging advances in microarray "chip" technology have allowed the parallel analysis of gene expression patterns for thousands of genes simultaneously. Sequence information derived from the genomes of many individuals is leading to the rapid discovery of single nucleotide polymorphisms or SNPs. Detection of these human polymorphisms will fuel the discipline of pharmacogenomics, resulting in an increase in the success of clinical trials, the rescue of drugs that have previously failed in clinical trials because of adverse reactions from patient subpopulations, and ultimately, in the development of more personalized drug therapies. The impending identification of all human genes will signal the end of the structural genomics phase and usher in the function genomics phase. Technologies have already begun to move toward high-throughput elucidation of gene relationships, interactions and, it is hoped, toward their functions.

Biotechnology↗

PubMed2002

Reduction of p53 gene expression in human primary hepatocellular carcinoma is associated with promoter region methylation without coding region mutation.

Functional inactivation of tumor suppressor genes during tumor progression has been shown to occur by either coding region mutation or promoter region methylation. Because of the functional equivalence of these two mechanisms, loss of tumor suppressor function generally occurs by one or the other mechanism, but rarely by both. Aberrant de novo methylation in most tumor suppressor promoter regions is found within CpG islands that occur near the transcription start site. The p53 promoter region is unique in that it does not contain a CpG island and therefore it is possible that methylation at critical CpG sites may be more important in gene silencing than total CpG methylation density. Other than site-specific aflatoxin B(1)-induced mutations, p53 coding region mutations are not frequently observed in most human primary hepatocellular carcinomas. In the present study, paired samples of human primary liver carcinoma and uninvolved tissue obtained from the same individual were evaluated for site-specific p53 promoter methylation status by methylation sensitive single nucleotide primer extension (Ms-SNuPE) and also for coding region mutations using polymerase chain reaction (PCR)- single strand conformation polymorphism (SSCP). The methylation pattern in the uninvolved tissue was variable at specific CpG sites, whereas the same sites had become highly methylated in tumor tissue from the same individual. Associated with de novo methylation, the level of p53 mRNA was significantly reduced in the tumor DNA relative to the uninvolved tissue DNA. None of the samples exhibited coding region mutations. Given that p53 mutations are rare in primary human liver tumors, these data suggest that transcriptional repression by p53 promoter methylation may contribute to tumor progression.

Carcinoma, Hepatocellular↗

PubMed1980

Maternal inheritance of human mitochondrial DNA.

Human mitochondrial DNA was obtained from peripheral blood platelets donated by the members of several independent families. The samples were screened for nucleotide sequence polymorphisms between individuals within these families. In each family in which we were able to detect a distinctly different restriction endonuclease cleavage pattern between the parents, the progeny exhibited the maternal cleavage pattern. Informative polymorphisms were detected for Hae II (PuGCGCPy) in a three-generation family composed of 33 members, for HincII (GTPyPuAC) in a two-generation family composed of four members, and for Hae III(GGCC) in a two-generation family composed of four members. The Hae II polymorphism was analyzed through all three generations in both the maternal and paternal lines. The results of this study demonstrate that human mitochondrial DNA is maternally inherited. The techniques described for using peripheral blood platelets as a source of human mitochondrial DNA represent a convenient way to obtain data on mitochondrial DNA variation in both individuals and populations.

Blood Platelets↗

PubMed1992

Polymerase-chain-reaction-based analysis of polymorphism in the HLA-B gene.

The polymerase chain reaction (PCR) in combination with the sequence-specific oligonucleotide probe (SSOP) was applied to analyze the polymorphism in the exon 2 of the HLA-B gene. In this study, genomic DNAs from 85 B-lymphoblastoid cell lines homozygous for HLA and peripheral blood granulocytes of 156 Japanese individuals were investigated. Two HLA-B-specific 5'-sided primers (CG4 and CG5) and two 3'-sided primers (CG2 and CG3) were designed for specific amplification of the exon. HLA-B alleles were classified into two groups (groups I and II) according to specific amplification with two types of the 3'-sided primers. The amplified DNAs were hybridized with 23 nonradioactively labeled SSOPs. Based on the hybridization patterns with the SSOPs, 34 HLA-B specificities were divided into 26 epitope combination (EC) groups. Fifteen HLA-B specificities were classified into four EC groups and these HLA-B specificities could not be distinguished from one another in the same EC group. Another 16 HLA-B specificities corresponded one by one to 16 distinct EC groups, and two subtypes of HLA-Bw75, B27, and Bw48 were also identified enabling the accurate typing of 22 HLA-B alleles at the DNA level. Single-strand conformation polymorphism (SSCP) of the PCR products from group I HLA-B alleles was also investigated. The HLA-B alleles showed distinct electrophoretic patterns in nondenaturing polyacrylamide gels, depending on the nucleotide sequences of the exon 2, indicating that the SSCP analysis may be an alternative, useful and practical HLA-matching system of HLA-B specificity in tissue transplantation.

Alleles↗

PubMed2001

Human endothelial cell-derived nuclear proteins that recognise polymorphic DNA elements in the von Willebrand factor gene promoter include YY1.

Four common base-change polymorphisms have been found in the von Willebrand factor gene promoter: (-1793 C/G, -1234 T/C, -1185 G/A and -1051 A/G). All four polymorphisms are in strong linkage disequilibrium and recent reports have indicated these polymorphisms are associated with plasma vWF:Ag levels suggesting that one or more of these elements influence regulation of the vWF gene. We report that human endothelial cell-derived trans-acting factors display allelic preferences in binding activity to each polymorphic site. The common A allele variant of the -1051 polymorphism and the rarer A allele variant of the -1185 polymorphism provided specific binding of nuclear proteins. The G allele counterpart of these two variants did not produce any complex formation indicating that the nucleotide substitution at these positions alters the DNA binding ability of nuclear factors. The two alleles of the -1234 polymorphism produced two complexes with a similar migration pattern however stronger binding was found to the common T variant of this allele. Two specific complexes associated with the rarer G allele of the -1793 polymorphism, but only one associated with the C allele. Supershift experiments revealed that the trans-acting factor YYI recognised the slower migrating complex formed on the -1234 T/C and the -1051 A polymorphic sites with a strong binding preference for the -1234 T allele variant. The identification of YY1 as a component of the factors that recognise these elements suggests that this ubiquitous nuclear protein may play a role in the regulation of the vWF promoter.

Base Sequence↗

PubMed1993

Estimates of linkage disequilibrium and the recombination parameter determined from segregating nucleotide sites in the alcohol dehydrogenase region of Drosophila pseudoobscura.

The alcohol dehydrogenase (Adh) region of Drosophila pseudoobscura, which includes the two genes Adh and Adh-Dup, was used to examine the pattern and organization of linkage disequilibrium among pairs of segregating nucleotide sites. A collection of 99 strains from the geographic range of D. pseudoobscura were nucleotide-sequenced with polymerase chain reaction-mediated techniques. All pairs of the 359 polymorphic sites in the 3.5-kb Adh region were tested for significant linkage disequilibrium with Fisher's exact test. Of the 74,278 pairwise comparisons of segregating sites, 127 were in significant linkage disequilibrium at the 5% level. The distribution of five linkage disequilibrium estimators D(ij), D2, r(ij), r2 and D(ij) were compared to theoretical distributions. The observed distributions of D(ij), D2, r(ij) and r2 were consistent with the theoretical distribution given an infinite sites model. The observed distribution of D(ij) differed from the theoretical distribution because of an excess of values at -1 and 1. No spatial pattern was observed in the linkage disequilibrium pattern in the Adh region except for two clusters of sites nonrandomly associated in the adult intron and intron 2 of Adh. The magnitude of linkage disequilibrium decreases significantly as nucleotide distance increases, or a distance effect. Adh-Dup had a larger estimate of the recombination parameter, 4Nc, than Adh, where N is the effective population size and c is the recombination rate. A comparison of the mutation and recombination parameters shows that 7-17 recombination events occur for each mutation event. The heterogeneous estimates of the recombination parameter and the inverse relationship between linkage disequilibrium and nucleotide distance are no longer significant when the two clusters of Adh intron sites are excluded from analyses. The most likely explanation for the two clusters of linkage disequilibria is epistatic selection between sites in the cluster to maintain pre-mRNA secondary structure.

Alcohol Dehydrogenase↗