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PubMed2006

Genetic variation in IGF1, IGF-1R, IGFALS, and IGFBP3 in breast cancer survival among Chinese women: a report from the Shanghai Breast Cancer Study.

Disruption of the balance of IGF (Insulin like growth factor) pathway constituents has been implicated in the etiology and progression of breast and other cancers. We hypothesized that genetic polymorphisms in IGF system members may be associated with breast cancer survival and evaluated this hypothesis in a cohort of 1,455 women diagnosed with breast cancer between 1996 and 1998 in Shanghai, China. Nineteen functional or potentially functional polymorphisms were evaluated in the IGF-1, IGF-1R, IGFALS, and IGFBP3 genes. Disease recurrence and vital status were obtained with a median follow-up time of 7.1 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Overall, no significant association was noted between any of the 19 polymorphisms and survival. However, subgroup analyses demonstrated apparent interactions between menopausal status and survival for several (Single nucleotide polymorphism) SNPs in the IGF-1R and IGFBP3 genes. Carriers of the A/G or G/G genotypes (rs951715) in the IGF-1R gene had an increased risk of death among post-menopausal women (HR = 1.7, 95% CI = 1.1-2.7). Significant associations with breast cancer survival in pre-menopausal women were found for two IGFBP3 polymorphisms (rs2854744 and rs3110697), with an additional polymorphism (rs6413441) reaching borderline significance (P = 0.05). Hazard ratios for overall survival among pre-menopausal women were 1.5 (95% CI = 1.1-2.0) for the C/T-T/T genotypes (rs3110697), 1.4 (95% CI = 1.0-1.9) for the A/C-C/C genotypes (rs2854744), and 1.4 (95% CI = 1.0-1.9) for the N/A-A/A genotypes (rs6413441). Taken together, these data suggest that polymorphisms in the IGF-1R and IGFBP3 genes may be associated with altered survival among subgroups of breast cancer patients defined by menopausal status.

Adult↗
PubMed2001

Genetic variation among the Golla pastoral caste subdivisions of Andhra Pradesh, India, according to the HLA system.

The HLA allele frequency distributions have been characterized for the HLA class I and class II loci of the Golla pastoral caste, from Southeast India, subdivided into the subcastes (Puja, Punugu, Kurava, Pokanati, Karnam, and Doddi). Genetic distances, neighbor-joining, correspondence, and haplotype analyses all indicate that the subcastes exhibit a high haplotype variability and that their genetic substratum may be the result of European-Middle East/Asian admixture with the autochthonous populations. The Karnam subcaste seems to be the one that has undergone a higher degree of admixture, when compared with the other subcastes. The Golla speak an old Indian Dravidian language and should theoretically represent the basic Indian substratum that existed before the postulated "Aryan" invasion.

Adult↗
PubMed1998

Genetic variation within a parthenogenetic lineage.

A clone of the grain aphid Sitobion avenae F. was maintained parthenogenetically over thirty-two generations (n = 344) in a constant environment: a new generation being set up by a female selected at random from the preceding generation. Genomic DNA from individual aphids was screened for genetic stability using RAPD-PCR with a previously tested ten-mer primer. A putative germ-line mutation was noted in generation 14 and somatic mutations were noted in generations 12, 25, 27 and 29. There were no differences in the RAPD-PCR profiles of winged and wingless morphs and samples tested for symbiotic DNA. No endoblotic fungal organism was associated with the clone. Southern blotting and hybridization studies indicated that band additions were of aphid origin. However, the RAPD-PCR profiles of the germ-line and somatic mutation samples were unique from other aphid clones cultured during the experimental period. This paper documents discernible genetic changes occurring within an animal clonal lineage over time and Impacts on the consequences this may have for clonal systems.

Animals↗
PubMed1978

Genetic variation at a locus (TAM-1) for submaxillary gland protease in the mouse and its location on chromosome No. 7.

Electrophoretic and activity variants for a testosterone-induced esteroprotease have been discovered in submaxillary glands from inbred strains of mice. The enzyme is tentatively designated tamase [TAM-1] and the variant genetic locus is Tam-1. The alleles Tam-1a and Tam-1b determine electrophoretically distinct zones of tamase activity, while Tam-lc produces no detectable enzyme activity. Data from recombinant inbred strains and B6AF1 X B6 and B6D2F1 X B6 backcrosses established linkage of Tam-1 to glucose phosphate isomerase (Gpi-1), pink-eyed dilution [p] and beta-hemoglobin (Hbb) on chromosome 7. The gene order is Gpi-1--Tam-1--p--HBB. Analysis of congenic resistant strains indicates that Tam-1 is closely linked to the minor histocompatibility locus, H-4. TAM-1 was not cross-reactive with antisera to mouse nerve growth factor, submaxillary renin, or tamases A and D.

Animals↗
PubMed1977

Genetic variation in the RNA transcripts of endogenous virus genes in uninfected chicken cells.

Uninfected cells from two different phenotypes of chicken embryos express significant amounts of endogenous viral information, though they do not produce virus particles. Cells of the phenotype gs(+)chf(+) are positive for both group-specific (gs) antigens and chicken helper factor (chf) activity, whereas cells of a second phenotype, gs(L)chf(+)(h(E)), demonstrate noncoordinate expression of these two viral activities (very low amounts of gs antigens, but extremely high helper activity). RNA from these cells was analyzed to determine the size, genetic content, and relative abundance of virus-specific RNAs in cells of each phenotype. Two major size classes of polyadenylic acid-containing RNA, homologous to the avian leukosis virus genome, were detectable in cells of both types. The larger RNA, which contained most of the sequences of the leukosis virus genome, was of different sizes in the two phenotypes, 31S in gs(+)chf(+) cells but 35S in the noncoordinate cell type. Analysis of the viral RNA with gene-specific complementary DNA probes revealed the following characteristics. (i) The 31S RNA appeared to lack portions of the gag and pol genes. (ii) A smaller RNA species, which sedimented at 21S in both cell types, was a transcript of the 3'-proximal portion of the viral genome, consisting of the env gene and the "common" sequences. (iii) The amount of env-specific RNA in the 21S region was more than six times higher in the noncoordinate cell type than in the gs(+)chf(+) cells; this difference was concordant with the 5- to 10-fold higher chf activity in the noncoordinate cells. (iv) The endogenous viral RNA in uninfected cells and the RNA from Rous-associated virus-0 virions hybridized only partially with DNA complementary to the common region of the Rous-associated virus-2 genome, whereas the RNA of all exogenous viruses tested hybridized almost completely to this complementary DNA. Small amounts of src-specific polyadenylated RNA were also present in uninfected chicken cells. This RNA sedimented as a single peak at 26S and was not covalently linked to any other identifiable virus-specific RNA sequences. The amount of src RNA was the same in the above two types of expression-positive cells and also in cells that were gs(-)chf(-), indicating that the transcription of the cellular sequences homologous to the src gene is independent of the transcription of the other endogenous viral genes.

Animals↗
PubMed2005

Genetic variation in the Desert Springsnail (Tryonia porrecta): implications for reproductive mode and dispersal.

Allozymes and mitochondrial cytochrome c oxidase subunit I (mtCOI) sequences were analysed to determine whether populations of the western North American gastropod Tryonia porrecta (from California, Nevada, Utah, and northwest Mexico) are strongly differentiated in accordance with traditional interpretation of regional fauna as ancient relicts inhabiting isolated fragments of late Tertiary palaeodrainages. These data were also used to assess whether this species, for which males have not been recorded, is a rare example of a molluscan parthenogen. Both data sets strongly supported monophyly of T. porrecta populations. Five of the nine sampled populations consisted of a single monoallelic allozyme genotype while the others contained two to 10 distinct genotypes. Allozymic data for genetically diverse Utah populations provided evidence of clonal and sexual reproduction. mtCOI haplotypes of T. porrecta formed two subgroups which differed by 1.99-2.60%. The common haplotype was found in seven populations with rare haplotypes observed in single populations. Based on these results and an available mtCOI molecular clock for related hydrobiid snails, T. porrecta is interpreted as a primarily parthenogenetic species that undergoes occasional sexual reproduction and has accumulated substantial diversity following its mid-Pliocene to mid-Pleistocene origin. Our results also suggest that the distribution of present-day populations of these gill-breathing snails did not result from fragmentation of an ancient, well-integrated drainage but instead reflects overland colonization of habitats which only recently became available following desiccation of late Quaternary pluvial lakes.

Animals↗
PubMed2006

Vertebrate DNA transposon as a natural mutator: the medaka fish Tol2 element contributes to genetic variation without recognizable traces.

DNA-based transposable elements, or DNA transposons, transpose in a cut-and-paste fashion, involving excision from the chromosome. If this process affects the function of a host gene and the excision rate is high, any gene associated with such an element would clearly be in a genetically "unstable" state, and there are many examples of unstable genes in various organisms. However, none have hitherto been reported in vertebrates. We here document the finding of an unstable mutant gene in the medaka fish, Oryzias latipes, a useful model animal for vertebrate genetics and evolutionary studies. In an inbred strain, excision of the Tol2 element inserted in a pigmentation gene occurs spontaneously, giving rise to different heritable phenotypes and new mutant genes that carry different excision footprint sequences. The phenotypic mutation rate is as high as 2% per gamete, representing a 1000-fold increase from spontaneous mutation rates so far determined with the same organism. With mutations caused by insertion, and then excision, of transposons, one can no longer recognize participation of transposons in their generation. Thus, the impact of DNA transposons on vertebrate genomes may be, and may have been, larger than commonly supposed.

Alleles↗
PubMed2006

Genetic variation and population differentiation in the lichen-forming ascomycete Xanthoria parietina on the island Storfosna, central Norway.

Genetic diversity and fine-scale population structure in the lichen-forming ascomycete Xanthoria parietina was investigated using sequence variation in part of the intergenic spacer (IGS) and the complete internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA. Sampling included 213 and 225 individuals, respectively, from seven populations in two different habitats, bark and rock, on the island Storfosna off the central west coast of Norway. Both markers revealed significant variation and a total of 10 IGS and 16 ITS haplotypes were found. There were no signs of significant positive spatial autocorrelation at any spatial size class down to 10% of transect length, nor did we find significant deviations from neutrality or signs of historical population expansion. Analysis of molecular variance (amova) indicated that most of the genetic variance observed was within populations, but when populations were grouped according to habitat, more than a quarter of the variance was explained among groups. Pairwise comparisons of populations (F(ST), exact tests of population differentiation) revealed significant differentiation between populations in different habitats (on bark or rock), but not between populations in the same habitat. Haplotype networks show that internal and presumably old haplotypes are shared between habitats, whereas terminal haplotypes tend to be unique to a habitat, mostly bark. We interpret the observed pattern to mean that there is no evidence of restricted gene flow between populations in the same habitat at the present spatial scale (interpopulation distances one or a few kilometres). On the other hand, differentiation between habitats is considerable, which we attribute to restricted gene flow between habitats (habitat isolation). Evidence suggests that the observed differentiation did not evolve locally. Estimates of divergence time between populations in the respective habitats indicate that an ancestral population started to diverge at least 34,000 years ago but probably much further back in time.

Ascomycota↗
PubMed1995

Genetic variation of apolipoprotein B can produce both low and high levels of apoB-containing lipoproteins in plasma.

The polymorphic markers of the apolipoprotein B (apoB) gene include restriction fragment length polymorphisms (RFLPs) scattered along the length of the gene, an insertion/deletion (I/D) polymorphism at the 5' and variable numbers of tandem repeats (VNTRs) at the 3' untranslated ends. The Xbal and I/D polymorphisms which do not affect apoB structure, produce modest effects on fasting and postprandial lipids and on responsiveness to dietary lipids, but the effects are population, age and gender-dependent. Much larger effects on fasting lipid levels are produced by structural mutations of the apoB gene. The apoB 3500 mutation affecting the low density lipoprotein (LDL) receptor recognition region of apoB-100, is one of the causes of the autosomal codominant familial hypercholesterolemia phenotype, characterized by fasting LDL elevations and atherosclerosis. Neither fasting nor postprandial hypertriglyceridemia are consistently present. Some forms of familial hypobetalipoproteinemia (FHBL) are genetically linked to various truncation-producing mutations of the gene. To date approximately 30 deletion, insertion or non-sense mutations have been identified resulting in apoB truncations ranging in size from apoB-9 to apoB-89. FHBL segregates as an autosomal dominant trait. Heterozygotes have less than a 5th to 10th percentile levels while compound heterozygotes and true homozygotes have much less than 5th percentile levels of total and LDL cholesterol. Heterozygotes have no symptoms traceable to the gene defect. Alterations in the distributions of apoB truncations among the lipoproteins in plasma and in the metabolism of the lipoproteins containing apoB-truncations depend on the lengths of the truncations.

Apolipoproteins B↗
PubMed1993

Detection and analysis of genetic variation in Hordeum spontaneum populations from Israel using RAPD markers.

Randomly amplified polymorphic DNA (RAPD) markers were used to analyse genetic diversity within and between Hordeum spontaneum populations sampled from Israel. Nei's index of genetic differentiation was used to partition diversity into within and between population components. Fifty-seven per cent of the variation detected was partitioned within 10 H. spontaneum populations. Using principal component and multiple regression analysis, part of the variation detected between populations was seen to be associated with certain ecogeographical factors. Fifty-eight per cent of the distribution of the phenotypic frequencies of three RAPD phenotypes detected using a single primer in 20 H. spontaneum populations could be accounted for by four ecogeographical variables, suggesting adaptive variation at certain RAPD loci.

Alleles↗
PubMed2005

An analysis of genetic variation across the MBL2 locus in Dutch Caucasians indicates that 3' haplotypes could modify circulating levels of mannose-binding lectin.

Mannose-binding protein (MBL) is a critical component of innate immunity and provides first-line protection against pathogens. Both circulating MBL serum levels and functional activity have been correlated with common genetic variants in the MBL2 gene. Associations between MBL deficiency and severe infections have been reported in immuno-incompetent patients and for autoimmune disorders; however, measured MBL serum levels do not fully correlate with the 'secretor haplotypes'. Previously, the MBL2 locus was resequenced and determined that a recombination hotspot divides MBL2 into two haplotype blocks. It was sought to investigate whether additional variants, in either block structure could associate with MBL serum levels. Therefore, 31 common variants were analysed across the locus in 212 DNA samples of healthy Caucasian individuals with known MBL serum concentrations. The additional 5' variants were in strong linkage to the elements of the 'secretor haplotypes'; functional alleles B, C and D also lie on restricted haplotypes. Four variants in the 3' block (Ex4-1483T>C, Ex4-1067G>A, Ex4-901G>A and Ex4-710G>A) are components of a distinct haplotype block. The results of this study suggest that additional 5' variants as well as markers of distinct 3' haplotype blocks in MBL2 may contribute to circulating protein levels, but further studies are required to confirm these observations. Last, there could be a selective advantage for diversification of the 3' region of the gene.

Adolescent↗
PubMed1991

Genetic variation in the time of oviposition in the laying hen.

1. The distribution of oviposition times in modern layers is relatively narrow. Consequently, in management systems where hens have to compete for nestboxes, some eggs will be laid on the floor. 2. The purpose of this study was to investigate the possibility of using genetic methods to change oviposition time while maintaining a high production rate. 3. The mean oviposition times of 464 hens from three selection lines were calculated using time-of-lay records for every egg laid until the hens reached 51 weeks of age. 4. Heritability estimates for mean oviposition time were high for each of the three lines: 0.38, 0.68 and 0.78. 5. The three lines differed in terms of the genetic correlations between mean oviposition time and certain important production traits. It should, however, be possible to shift the mean oviposition time while maintaining a high production rate. 6. It is suggested that the spread in oviposition times be increased by performing divergent selection for mean oviposition time and by mixing the different genotypes in the same commercial flock, kept on the floor or in other non-cage systems.

Animals↗
PubMed1998

[Genetic variation of MSX1 has a sexual dimorphism in non syndromic cleft palate in the Chilean population].

BACKGROUND: Recent studies in mice have demonstrated that the Msx-1 homebox gene is implicated in cleft palate. Thus, it has been suggested that its human homologue, MSX1 (HOX-7), located in chromosome 4 could be involved in the etiology of non syndromic cleft lip palate. AIM: To study the linkage between non syndromic cleft palate and variations of MSX1 gene. PATIENTS AND METHODS: Seventy three patients with non syndromic cleft lip palate (34 simplex and 37 multiplex), 127 unaffected relatives of the cases (61 relatives of simplex cases and 66 relatives of multiplex cases) and 77 controls were studied. DNA was extracted from leukocytes and the intragenic microsatellite sequence was amplified by PCR. RESULTS: A polymorphism of four alleles was observed, 1 (175 bp), 2 (173 bp), 3 (171 bp) and 4 (169 bp). Alleles 2 and 4 showed a joint variation in males with multiplex cleft lip palate and in their respective unaffected male relatives, that was significant when compared with male controls. Instead, the joint variation of alleles 1 and 4 of unaffected female relatives had significant differences with female controls. Females with multiplex cleft lip palate differed from female controls only in allele 1. CONCLUSIONS: These results support the hypothesis of a genetic heterogeneity in the etiology of non syndromic cleft lip palate.

Alleles↗
PubMed2000

Genetic variations of the hepatic lipase gene in Korean patients with coronary artery disease.

OBJECTIVES: To investigate the association between the HL gene (LIPC) polymorphism, plasma lipid levels and coronary artery disease (CAD). DESIGN AND METHODS: One hundred thirty-seven subjects with CAD and 124 age-matched controls were examined by polymerase chain reaction (PCR). The PCR products were analyzed for LIPC genotyping by enzyme digestion. RESULTS: The allele frequencies of the three polymorphisms in the LIPC gene were not significantly different between the controls and CAD patients. The + allele of the -514 promoter polymorphism was associated with higher total cholesterol (p = 0.05), apolipoprotein (apo) AI (p = 0.04) levels in the men of the normal group, and the apoB level (p = 0.03) in the women of the CAD group without allele effect. The allele frequencies of the -250 and -514 promoter polymorphisms of Koreans were significantly different from those of the white and African American populations studied (p < 0.05). CONCLUSIONS: The -514 promoter polymorphism may fluctuate on the lipid levels due to linkage disequilibria with other polymorphisms of the LIPC gene or nearby genes. The difference of the -250 promoter allele frequencies among the different populations may partially explain the variation of the HDL levels in ethnic groups. To elucidate the more exact associations of LIPC polymorphism with the plasma lipid levels, the precise biochemical mechanisms of the LIPC alleles are required.

Aged↗