SEARCH · PubMed Health

Results for “Single locus”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 397 records · Page 22Linked to original sources

PubMed2001

Comparison of 'model-free' and 'model-based' linkage statistics in the presence of locus heterogeneity: single data set and multiple data set applications.

Earlier work [Knapp et al.: Hum Hered 1994;44:44-51] focusing on affected sib pair (ASP) data established the equivalence between the mean test and a test based on a simple recessive lod score, as well as equivalences between certain forms of the maximum likelihood score (MLS) statistic [Risch: Am J Hum Genet 1990;46:242-253] and particular forms of the lod score. Here we extend the results of Knapp et al. [1994] by reconsidering these equivalences for ASP data, but in the presence of locus heterogeneity. We show that Risch's MLS statistic under the possible triangle constraints [Holmans: Am J Hum Genet 1993;52:362-374] is locally equivalent to the ordinary heterogeneity lod score assuming a simple recessive model (HLOD/R); while the one-parameter MLS assuming no dominance variance is locally equivalent to the (homogeneity) recessive lod. The companion paper (this issue, pp 199-208) showed that when considering multiple data sets in the presence of locus heterogeneity, the HLOD can suffer appreciable losses in power. We show here that in ASP data, these equivalences ensure that this same loss in power is incurred by both forms of the MLS statistic as well. The companion paper also introduced an adaptation of the lod, the compound lod score (HLOD/C). We confirm that the HLOD/C maintains higher power than these 'model-free' methods when applied to multiple heterogeneous data sets, even when it is calculated assuming the wrong genetic model.

Chromosome Mapping↗

PubMed1995

Mathematical limits of multilocus models: the genetic transmission of bipolar disorder.

We describe a simple, graphical method for determining plausible modes of inheritance for complex traits and apply this to bipolar disorder. The constraints that allele frequencies and penetrances lie in the interval 0-1 impose limits on recurrence risks, KR, in relatives of an affected proband for a given population prevalence, KP. We have investigated these limits for KR in three classes of relatives (MZ co-twin, sibling, and parent/offspring) for the general single-locus model and for two types of multilocus models: heterogeneity and multiplicative. In our models we have assumed Hardy-Weinberg equilibrium, an all-or-none trait, absence of nongenetic resemblance between relatives, and negligible mutation at the disease loci. Although the true values of KP and the KR's are only approximately known, observed population and family data for bipolar disorder are inconsistent with a single-locus model or with any heterogeneity model. In contrast, multiplicative models involving three or more loci are consistent with observed data and, thus, represent plausible models for the inheritance of bipolar disorders. Studies to determine the genetic basis of most bipolar disorder should use methods capable of detecting interacting oligogenes.

Alleles↗

PubMed1981

Pedigree analysis of Hodgkin's disease in a Newfoundland genealogy.

An extensive Newfoundland genealogy shows a large number of cases of lymphoreticular malignancies. A recessive pattern of inheritance had been previously suggested, but no quantitative investigation of the hypothesis was made. Here we have investigated a variety of aspects of the descent structure of the pedigree and shown that for only a subset of the traits can the inference be upheld. For Hodgkin's disease (HD) and generalized immunodeficiency (ID) there is clear evidence for a recessive HD/ID susceptibility allele. The remainder do not follow this pattern, show no evidence of a single-locus effect and little of any genetic effect. The ancestry of the HD/ID cases was therefore investigated in detail, and likelihoods computed on the pedigree. These confirmed the recessive nature of the trait, as also did the risk analysis which quite clearly identified the paths of descent taken by the allele. The determination of these paths is a prerequisite for any linkage analysis which might further confirm the single-locus nature of the trait.

Female↗

PubMed1997

The sib-pair problem. I. Affected pairs with parents. Constant penetrance models.

Affected sib pairs with typed but unaffected parents, conveniently termed foursomes, have become a major source of information on genetic susceptibility to common disease. So far most methods of analysis have been based on extensions of the single locus analyses developed, and successfully applied, to the mendelian disorders. However, unifactorial methods are not suited to multifactorial disorders. The power of methods of detecting linkage in the presence of more than one locus with one or more susceptibility alleles is considered. The relevance of familial clustering to predicting the presence of loci with susceptibility or resistance alleles sufficiently frequent and effective to have an appreciable influence on population incidence is discussed. The mathematical problem of clustering due to numerous alleles of small effect was resolved by Pearson in 1901 in relation to claims that the mendelian model of an allele at a single locus determining a distinct phenotype was necessary to explain the familial concentrations that had been observed in several species. The apparent inconsistency between the mendelian and polygenic models was resolved by Fisher's demonstration in 1918 that there was no essential difference between these two extreme forms of phenotypic determination. Although constant penetrance models are unrealistic, and no longer necessary since Pearson's analysis, the assumption is implicit in most recent analyses and has the advantage of simplicity in providing a lower limit on the sample sizes necessary.

Disease Susceptibility↗

PubMed1984

An application of a model for a genotype-dependent relationship between a concomitant (age) and a quantitative trait (LDL cholesterol) in pedigree data.

In most genetic studies in humans the variability in a quantitative trait is adjusted for variability in concomitants (age, sex, etc) using a single regression equation prior to analyses of pedigree data. To illustrate an alternative approach, a single locus genetic model was tested. This model incorporates genotypic effects on the level of the trait, the variability in the trait, and the relationship between a concomitant and the trait. In this study, the model was applied to measures of age and low-density lipoprotein (LDL) cholesterol in a large kindred with familial hypercholesterolemia. The application of this model to 322 individuals in four generations provided evidence that genotypic variation at a single locus influences LDL levels early in life, the rate of increase of LDL with age and the phenotypic variance. A model with genotype-dependent slope and variance fit the data significantly better than a model with slope and variance independent of genotype. The inclusion of age-specific genotypic differences contributed to identification of high-risk individuals, to statistical support for a major locus, and to evidence for genetic determination of the tracking of LDL levels. Models that incorporate genotype-specific concomitant effects have the potential to represent more realistically the relationship between genotypic variability and quantitative phenotypic variation than models that assume that these effects do not exist.

Adolescent↗

PubMed1998

Likelihood-based inference for the genetic relative risk based on affected-sibling-pair marker data.

Using genetic marker data from affected sibling pairs, we study likelihood-based linkage analysis under quasi-recessive, quasi-dominant, and general single-locus models. We use an epidemiologic parameterization under a model where the marker locus is closely linked to the putative disease susceptibility gene. This model and parameterization allow inferences about the relative risk associated with the susceptible genotype. We base inferences on approximate likelihoods that focus on the affected siblings in the sibship and, using these likelihoods, we derive closed-form maximum likelihood estimators for model parameters and closed-form likelihood ratio statistics for tests that the relative risk associated with the susceptible genotype is one. Under the general single-locus model, our likelihood ratio test is the same as the iteratively computed triangle test proposed by Holmans (1993, American Journal of Human Genetics 52, 362-374) for the case where marker identity-by-descent is known; our derivation gives a closed form for the test statistic. We present quartiles of the distribution of parameter estimates and critical values for the exact null distribution of our likelihood ratio test statistics; we also give large-sample approximations to their null distributions. We show that the powers of our likelihood ratio tests exceed the powers of more commonly used nonparametric affected-sibling-pair tests when the data meet the inheritance model assumptions used to derive the test; we also show that our tests' powers are robust to violation of model assumptions. We conclude that our model-based inferences provide a practical alternative to more common affected-sibling-pair tests when investigators have some knowledge about the mode of inheritance of a disease and that our methods may sometimes be useful for comparing the genetic relative risk with environmental relative risks.

Disease Susceptibility↗

PubMed1998

Evidence for major genetic control of wheeze in relation to history of respiratory allergy: Humboldt family study.

We report the results of segregation analyses for wheeze before and after a history of respiratory allergy was taken into consideration. The analyses were based on data from 309 nuclear families with 1,053 individuals living in the town of Humboldt, Saskatchewan in 1993, and were performed by using the REGD program of the SAGE package. For adults, information on wheeze and history of respiratory allergy was provided by themselves, and for children, by their parents. Segregation analyses were first conducted before adjustment for history of respiratory allergy. Other covariates were adjusted including sex, current smoking, household exposure to tobacco smoke, and type of house. A single locus model with residual familial effects fit the data well, but none of the Mendelian models (recessive, dominant, and codominant) could be distinguished. The no-parent-offspring-transmission hypothesis was rejected. However, when the variable of respiratory allergy was included in the models as a covariate, both Mendelian and environmental hypotheses were rejected. The Mendelian model had a relatively lower value of Akaike's Information Criterion than did the environmental model (1095.56 versus 1111.24). The data suggest that a single locus gene explains a portion of wheeze that is related to respiratory allergy, and that common environmental factors and/or polygenes also account for a certain familial aggregation of wheeze.

Adolescent↗

PubMed1994

DNA fingerprinting used to test for family effects on precocious sexual maturation in two populations of Oncorhynchus tshawytscha (Chinook salmon).

Two single locus Variable Number Tandem Repeat (VNTR) DNA probes were used to test for differences in allele distribution between precociously mature male and immature chinook salmon, Oncorhynchus tshawytscha. Two populations were examined: Robertson Creek (RC) adult salmon, and Nicola River (NR) freshwater juveniles, or parr. Genomic DNA was extracted from 74 RC precociously mature adult males ('jacks') and 94 RC immature adults of the same age and from 45 NR precociously mature parr and 51 NR nonmaturing parr. The genomic DNA was hybridized with a single locus VNTR probe developed for chinook salmon (OtSL1), as well as one developed for Atlantic salmon, Salmo salar (Ssa1). The allele frequency distributions at both loci were significantly different for the RC jacks and immature fish, indicating a family effect on the incidence of precocious maturation in that population. No difference was found between the allele frequency distribution of the NR precocious and immature parr. A bin width sensitivity analysis showed that the comparisons of the allele frequency distributions were insensitive to the choice of bin size. No differences in heterozygosity were found between mature and immature fish at either locus for both stocks. Preliminary testing for family effects on phenotypes of interest, such as alternative life history strategies, can be performed using hypervariable VNTR DNA probes, prior to implementing costly and involved breeding programmes.

Alleles↗

PubMed1992

Murine alpha 1,3-galactosyltransferase. A single gene locus specifies four isoforms of the enzyme by alternative splicing.

We have reported the characterization of a cDNA (clone 31A) encoding bovine alpha 1,3-galactosyltransferase (alpha 1,3-GT) (Joziasse, D. H., Shaper, J. H., Van den Eijnden, D. H., Van Tunen, A. J., and Shaper, N. L. (1989) J. Biol. Chem. 264, 14290-14297). With the goal of isolating a full-length cDNA encoding murine alpha 1,3-GT we screened a cDNA library with clone 31A and isolated a 3.4-kilobase (kb) alpha 1,3-GT clone (4A). The murine coding sequence is 78% similar to that of the bovine alpha 1,3-GT cDNA, but the "stem" region (defined as the region that links the single transmembrane domain to the catalytic domain) of the murine alpha 1,3-GT encoded by clone 4A, is 31 amino acids shorter than the corresponding region of the bovine alpha 1,3-GT. To screen for heterogeneity in the murine alpha 1,3-GT transcripts, we carried out a polymerase chain reaction (PCR) analysis on mouse C127 cDNA. Four distinct transcripts were detected, which predict four isoforms of the alpha 1,3-GT polypeptide that differ only in the length of their stem region. To determine how the four different transcripts are generated from a single gene, we have established the genomic organization for murine alpha 1,3-GT. The full-length mRNA spans at least 35 kb of genomic DNA and is distributed over nine exons that range in size from 36 base pairs (bp) to approximately 2600 bp. The protein coding region is distributed over six exons, and the 5'-untranslated sequence is distributed over three exons. Comparison of the genomic DNA sequence with that of the four different mRNAs indicates that these transcripts are produced by alternative splicing of the murine pre-mRNA according to a cassette model. A tissue survey using RNA-PCR revealed the presence of four different alpha 1,3-GT transcripts in all mouse tissues and cell lines examined to date, with the notable exception of male germ cells. Additionally, although alpha 1,3-GT levels increased upon thioglycollate-induced activation of mouse peritoneal macrophages, the ratio of the alpha 1,3-GT isoforms was essentially unchanged. Similar results were obtained upon retinoic acid-induced differentiation of murine F9 teratocarcinoma cells. Lastly, a similar PCR analysis of bovine cDNA produced only a single DNA fragment, corresponding to bovine cDNA clone 31A.

Amino Acid Sequence↗

PubMed1991

Additional microsatellite markers for mouse genome mapping.

Mouse sequence information from the EMBL and GenBank databases, published sequences and genomic clones have been analyzed for simple repetitive elements or microsatellites. Each microsatellite has been amplified by the polymerase chain reaction (PCR) as a single locus marker. PCR primers were designed from unique sequence flanking each repeat. Size variation of PCR products less than 750 base pairs (bp) between mouse strains has been determined using ethidium bromide-stained acrylamide or agarose gels. A further 74 newly characterized microsatellites are presented in this paper, bringing to 185 the total we have analyzed. Of these, 157/185 (85%) have more than one allele, 143/178 (80%) vary in length between C57BL/6J and Mus spretus, and 82/168 (49%) vary between DBA/2J and C57BL/6J. Microsatellites provide informative single locus probes for linkage analysis in the construction of a genetic map of the mouse genome.

Animals↗

PubMed2000

Genotypic diversity and gene flow in brooding and spawning corals along the Great Barrier Reef, Australia.

Marine organisms exhibit great variation in reproductive modes, larval types, and other life-history traits that may have major evolutionary consequences. We measured local and regional patterns of genetic variation in corals along Australia's Great Barrier Reef to determine the relative contributions of sexual and asexual reproduction to recruitment and to infer levels of gene flow both locally (among adjacent sites, < 5 km apart) and regionally (among reefs separated by 500-1,200 km). We selected five common brooding species (Acropora cuneata, A. palifera, Pocillopora damicornis, Seriatopora hystrix, and Stylophora pistillata) and four broadcast spawners (Acropora hyacinthus, A. cytherea, A. millepora, and A. valida), which encompassed a wide range of larval types and potential dispersal capabilities. We found substantial genotypic diversity at local scales in six of the nine species (four brooders, two spawners). For these six, each local population displayed approximately the levels of multilocus genotypic diversity (Go) expected for outcrossed sexual reproduction (mean values of Go:Ge ranged from 0.85 to 1.02), although consistent single-locus heterozygous deficits indicate that inbreeding occurs at the scale of whole reefs. The remaining three species, the brooder S. hystrix and the spawners A. valida and A. millepora displayed significantly less multilocus genotypic diversity (Go) than was expected for outcrossed sexual reproduction (Ge) within each of several sites. Acropora valida and A. millepora showed evidence of extensive localized asexual replication: (1) a small number of multilocus (clonal) genotypes were numerically dominant within some sites (Go:Ge values were as low as 0.17 and 0.20): (2) single-locus genotype frequencies were characterized by both excesses and deficits of heterozygotes (cf. Hardy-Weinberg expectations), and (3) significant linkage disequilibria occurred. For the brooding S. hystrix Go:Ge values were also low within each of four sites (x = 0.48). However, this result most likely reflects the highly restricted dispersal of gametes or larvae, because levels of genetic variation among sites within reefs were extremely high (FSR = 0.28). For all species, we detected considerable genetic subdivision among sites within each reef (high FSR-values), and we infer that larval dispersal is surprisingly limited (i.e., Nem among sites ranging from 0.6 to 3.3 migrants per generation), even in species that have relatively long planktonic durations. Nevertheless, our estimates of allelic variation among reefs (FRT) also imply that for all four broadcast spawning species and three of the brooders, larval dispersal is sufficient to maintain moderate to high levels of gene flow along the entire Great Barrier Reef (i.e., Nem among reefs ranged from 5 to 31). In contrast, widespread populations of S. hystrix and S. pistilata (the two remaining brooders) are relatively weakly connected (Nem among reefs was 1.4 and 2.5, respectively). We conclude that most recruitment by corals is very local, particularly in brooders, but that enough propagules are widely dispersed to ensure that both broadcast spawning and brooding species form vast effectively panmictic populations on the Great Barrier Reef.

Animals↗

PubMed1994

Mass-spectrographic analysis of a porcine amelogenin identifies a single phosphorylated locus.

The amelogenins of the extracellular matrix of developing dental enamel, comprise a family of tissue-specific proteins which are postulated to play a central role in the biomineralization of dental enamel [1]. The primary structures of amelogenins derived from cow, pig, human, mouse and rat have now been elucidated by the interpretation of cDNA sequences or by direct amino acid sequence determinations [2-6] demonstrating a high degree of sequence homology between species [1]. However, the nature of post-translational modification of these proteins is less clear. In particular, early reports of amelogenin phosphorylation [7-8] have proved to be difficult to confirm by direct chemical analyses [1]. Using mass spectrographic analysis, we recently [9], reported that the lower molecular weight (5-7 kDa) bovine and porcine amelogenin polypeptides (TRAP and LRAP) contained a single phospho-serine residue at position 16Ser and, since these polypeptides are derived by proteolytic processing from the higher molecular weight "parent" amelogenins (18-25 kDa), we concluded that these precursor molecules must also be phosphorylated, as has previously been suggested [10]. In contrast to these observations, an extensive amino acid sequencing study of porcine amelogenins has recently reported no evidence for such phosphorylation [1]. We now report that a new analysis of the major porcine ("20K") amelogenin provides positive evidence for porcine amelogenin phosphorylation.

Amelogenin↗

PubMed1990

Linkage strategies for genetically complex traits. II. The power of affected relative pairs.

The power to detect disease-susceptibility loci through linkage analysis using pairs of affected relatives and affected-unaffected pairs is examined. Allelic identity by descent (ibd) for a completely polymorphic marker for sibling, uncle-nephew, grandparent-grandchild, half-sib, and first-cousin pairs is considered. Affected-unaffected pairs generally represent a poor strategy. For single-locus models, ibd depends on lambda R, the risk ratio for type R relatives compared with population prevalence, and the recombination fraction theta. The ibd for grandparent-grandchild pairs is least affected by recombination, followed by sibs, half-sib, uncle-nephew, and first-cousin pairs. For diseases with large lambda values and for small theta values, distant relatives offer greater power. For larger theta values, grandparent-grandchild pairs are best; for small lambda values, sibs are best. Additive and multiplicative multilocus models are considered. For the multiplicative model, the same formulas as in the single-locus model apply, except that lambda iR (for the ith contributing locus) is substituted for lambda R. For the additive model, the deviation from null expectation for ibd is divided among all contributing loci. Compared with the multiplicative model, for an additive model there is usually greater advantage in distant relationships. Multipoint analysis using linked marker loci for affected relative pairs is described. Simultaneous use of multiple markers diminishes the effect of recombination and allows for localization of the disease-susceptibility locus.

Alleles↗

PubMed2003

Association of single nucleotide polymorphisms of the bile salt export pump gene with intrahepatic cholestasis of pregnancy.

BACKGROUND: We determined whether genetic variability in the gene encoding the bile salt export pump (BSEP) contributes to individual differences in susceptibility to the development of intrahepatic cholestasis of pregnancy (ICP). METHODS: The study involved 57 affected and 115 healthy control pregnant women who were genotyped for two single nucleotide polymorphisms (SNPs) in the BSEP gene. Chi-square analysis was used to assess genotype and allele frequency differences between the cholestatic and control groups. In addition, single locus analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, among the cholestatic and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, employing an expectation-maximization (EM) algorithm. RESULTS: The genotype and allele frequency distribution of the two intragenic SNPs in the ICP and control groups revealed significant evidence of association with the exon 28 SNP (P=0.04 and P=0.02, respectively). In addition, a borderline allele association was noted with the intron 19 SNP (P=0.08). Although the overall distribution of estimated haplotypes of intron 19 and exon 28 SNPs did not differ between the ICP and control groups, the most common haplotype, A-G, was significantly overrepresented in the ICP group (P=0.02), at an odds ratio of 1.73 (95% CI: 1.08-2.74). CONCLUSIONS: The use of two intragenic SNPs in both single locus and haplotype analyses of association suggests that the BSEP gene is a susceptibility gene in intrahepatic cholestasis of pregnancy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1995

Automated short tandem repeat (STR) analysis in forensic casework--a strategy for the future.

Short tandem repeat (STR) loci are routinely analysed for forensic purposes in the UK. Because small regions of DNa are amplified, successful results are more likely to be obtained from highly degraded material where the DNA fragment length may be < 500 bp. The method is superceeding conventional analysis with single locus probes (SLPs). Dimeric STR loci display stutter artefacts, hence STRs used in casework are restricted to tri or tetrameric loci. Some STRs are complex repeats and have more alleles than simple repeats - for example the locus D21S11 has 21 alleles which differ in size by 2 bp because of the presence/absence of a hexanucleotide within the block of tetrameric repeats. These loci are of great potential interest because they combine increased discriminating power with reduced potential to stutter. Multiplexing 4 different loci with different dye labelled primers (i.e. carrying out polymerase chain reaction of 4 loci simultaneously) using the ABD 373A automated sequencer enables a large numbers of samples to be processed. In addition data aquisition and manipulation is automated so that minimum postelectrophoresis operator input is required. It is our aim to develop a system equivalent in power to that of 4 single locus probes. To achieve this we have developed an octoplex system consisting of 7 loci and a sex test (amelogenin locus) which has a probability of chance of association of 10(-9); the power of this system is equivalent to that achieved by 4 conventional SLPs.

Alleles↗

PubMed1999

Analysis and interpretation of short tandem repeat microvariants and three-banded allele patterns using multiple allele detection systems.

The Palm Beach County Sheriffs Office (PBSO) Crime Laboratory and the Alabama Department of Forensic Sciences (ADFS) have validated and implemented analysis of short tandem repeat (STR) sequences on casework using silver staining kit and SYBR Green I detection systems and are presently validating fluorescently tagged STR alleles using the Hitachi FMBIO 100 instrument. Concurrently, the Broward County Sheriff's Office (BSO) Crime Laboratory is validating the ABI Prism310 Genetic Analyzer capillary electrophoresis STR detection system (ABI CE310) from Perkin Elmer Applied BioSystems. During the course of analyzing over 10,000 individuals for the STR loci CSF1PO, TPOX and THO1 (CTT) using silver staining for allele detection, 42 samples demonstrated alleles that were "off ladder," contained three-banded patterns at a single locus, or exhibited an apparent THO1 "9.3,10" allele pattern. PBSO, ADFS and BSO Crime Laboratories have collaborated on the verification of the allele patterns observed in these 42 samples using the following allele detection systems: (1) manual silver staining, (2) SYBR Green I staining, and/or (3) fluorescently tagged amplified products separated by polyacrylamide gel electrophoresis or capillary electrophoresis followed by laser detection. Regardless of the CTT allele detection system utilized, concordant results were obtained for 41 of the 42 samples. The only exception was a sample in which a wide band within the THO1 locus was identified as a THO1 "9.3, 10" genotype by silver staining kit and SYBR Green I staining but was verified to be a THO1 "9.3" homozygote by all other allele detection systems. Manual allele detection could readily identify microvariants, as a visual assessment of stained gels clearly shows that alleles do not migrate coincident with well-characterized allele size standards. As would be predicted, however, the manual detection systems did not provide adequate resolution to approximate the basepair size for off-ladder variants. All fluorescent software program systems were consistent in designating alleles "not in range" or "off ladder," thereby indicating true microvariants. All single-locus three-banded patterns were detected using all of the STR multiplex systems. In addition, individual locus-specific primers verified multiplexed amplified products were specific for the locus in question.

Alleles↗

PubMedDate not supplied

Genetics of alcohol dehydrogenase and aldehyde dehydrogenase from Monodelphis domestica cornea: further evidence for identity of corneal aldehyde dehydrogenase with a major soluble protein.

A didelphid marsupial, the gray short-tailed opossum (Monodelphis domestica), was used as a model species to study the biochemical genetics of alcohol dehydrogenases (ADHs) and aldehyde dehydrogenase (ALDH) in corneal tissue. Isoelectric point variants of corneal ALDH (designated ALDH3) and a major soluble protein in corneal extracts were observed among eight families of animals used in studying the genetics of these proteins. Both phenotypes exhibited identical patterns following PAGE-IEF and were inherited in a normal Mendelian fashion, with two alleles at a single locus (ALDH3) showing codominant expression. The data provided evidence for genetic identity of corneal ALDH with this major soluble protein, and supported biochemical evidence, recently reported for purified bovine corneal ALDH, that this enzyme constitutes a major portion of soluble corneal protein (Abedinia et al. 1990). Isoelectric point variants for corneal ADH were also observed, with patterns for the two major forms (ADH3 and ADH4) and one minor form (ADH5) being consistent with the presence of two ADH subunits (designated gamma and delta), and variant phenotypes existing for the gamma subunit. The genetics of this enzyme was studied in the eight families, and the results were consistent with codominant expression of two alleles at a single locus (designated ADH3). It is relevant that a major detoxification function has been proposed for corneal ADH and ALDH, in the oxidoreduction of peroxidic aldehydes induced by available oxygen and UV-B light (Holmes & VandeBerg, 1986a). In addition, a direct role for corneal ALDH as a UV-B photoreceptor in this anterior eye tissue has also been proposed (Abedinia et al. 1990).

Alcohol Dehydrogenase↗

PubMed2005

Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas.

B-cell leukaemia or lymphoma with a combination of t(8;14)(q24;q32) of Burkitt leukaemia/lymphoma and t(14;18)(q32;q21) of follicular lymphoma may present clinically as de novo acute lymphoblastic leukaemia or transformation of follicular lymphoma to aggressive histology diffuse lymphoma. A number of cell lines have been reported with a complex t(8;14;18) with fusion of MYC, IGH and BCL2 on the same derivative 8 chromosome. The objective of this study was to determine the frequency and chromosomal features of this der(8)t(8;14;18) in a series of acute leukaemias and malignant lymphomas. A database of 1350 leukaemia and lymphoma karyotypes was searched for cases with structural alterations affecting both 8q24 and 18q21. A total of 55 cases were identified, of which eight revealed a complex der(8)t(8;14;18) with an MYC-IGH-BCL2 rearrangement resulting from translocation of BCL2 and MYC with a single disrupted IGH allele. Molecular cytogenetic investigation is essential to identify cases of high-grade leukaemia/lymphoma with concurrent translocations affecting the BCL2 and MYC loci.

Adult↗