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At least 811 records · Page 45Linked to original sources
PubMed2004

Localization of a novel recessive powdery mildew resistance gene from common wheat line RD30 in the terminal region of chromosome 7AL.

Segregation analysis of resistance to powdery mildew in a F(2) progeny from the cross Chinese Spring (CS) x TA2682c revealed the inheritance of a dominant and a recessive powdery mildew resistance gene. Selfing of susceptible F(2) individuals allowed the establishment of a mapping population segregating exclusively for the recessive resistance gene. The extracted resistant derivative showing full resistance to each of 11 wheat powdery mildew isolates was designated RD30. Amplified fragment length polymorphism (AFLP) analysis of bulked segregants from F(3)s showing the homozygous susceptible and resistant phenotypes revealed an AFLP marker that was associated with the recessive resistance gene in repulsion phase. Following the assignment of this AFLP marker to wheat chromosome 7A by means of CS nullitetrasomics, an inspection of simple sequence repeat (SSR) loci evenly spaced along chromosome 7A showed that the recessive resistance gene maps to the distal region of chromosome 7AL. On the basis of its close linkage to the Pm1 locus, as inferred from connecting partial genetic maps of 7AL of populations CS x TA2682c and CS x Virest ( Pm1e), and its unique disease response pattern, the recessive resistance gene in RD30 was considered to be novel and tentatively designated mlRD30.

Ascomycota↗
PubMed2006

A cDNA-AFLP based strategy to identify transcripts associated with avirulence in Phytophthora infestans.

Expression profiling using cDNA-AFLP is commonly used to display the transcriptome of a specific tissue or developmental stage. Here, cDNA-AFLP was used to identify transcripts in a segregating F1 population of Phytophthora infestans, the oomycete pathogen that causes late blight. To find transcripts derived from putative avirulence (Avr) genes germinated cyst cDNA from F1 progeny with defined avirulence phenotypes was pooled and used in a bulked segregant analysis (BSA). Over 30,000 transcript derived fragments (TDFs) were screened resulting in 99 Avr-associated TDFs as well as TDFs with opposite pattern. With 142 TDF sequences homology searches and database mining was carried out. cDNA-AFLP analysis on individual F1 progeny revealed 100% co-segregation of four TDFs with particular AVR phenotypes and this was confirmed by RT-PCR. Two match the same P. infestans EST with unknown sequence and this is a likely candidate for Avr4. The other two are associated with the Avr3b-Avr10-Avr11 locus. This combined cDNA-AFLP/BSA strategy is an efficient approach to identify Avr-associated transcriptome markers that can complement positional cloning.

Chromosome Mapping↗
PubMed1984

Provisional assignment of MPI, PKM2, PGM3, and ME1 to Chinese hamster chromosome 4.

Concordant segregation analysis of Chinese hamster (Cricetulus griseus) isozymes and chromosomes segregating from hamster X mouse interspecific somatic cell hybrids revealed that loci for ME1, PGM3, MPI, and PKM2 are located on Chinese hamster chromosome 4. Synteny of these loci in hamsters provides additional evidence for the conservation of mammalian autosomal linkage groups.

Animals↗
PubMed2006

Does a pleiotropic gene explain deafness and blue irises in white cats?

The prevalence of deafness is high in cat populations in which the dominant white gene is segregating. The objective of this study was to investigate whether there is a gene that is responsible for deafness as well as for blue eyes and to establish a plausible mode of inheritance. For this purpose, data from an experimental colony with deaf cats were analyzed. The hearing status was determined by acoustically evoked brain stem responses (BAER). Complex segregation analyses were conducted to find out the most probable mode of inheritance using maximum likelihood procedures. The prevalence of deafness and partial hearing in the experimental colony was 67% and 29%, respectively. The results of the bivariate segregation analysis support the hypothesis of a pleiotropic major gene segregating for deafness and blue iris colour. The high heritability coefficients for both traits, 0.55 and 0.75 respectively, indicate that beside the major gene there is an important influence of polygenic effects.

Acoustic Stimulation↗
PubMed1998

Is there a link between African iron overload and the described mutations of the hereditary haemochromatosis gene?

Over 80%, of Caucasian patients with hereditary haemochromatosis are homozygotes for a C282Y mutation in the HFE gene on chromosome 6. Recent evidence suggests that a genetic factor may also be involved in the pathogenesis of African iron overload, although the locus has not been described. PCR analysis of DNA from 25 southern Africans, identified by segregation analysis as having a high probability of carrying the putative African iron-loading gene, failed to identify any subjects with the C282Y mutation. The possible genetic defect in African iron overload appears to be different from that described in most cases of hereditary haemochromatosis in Caucasians.

Adult↗
PubMed1983

Provisional assignment of TPI, GPI, and PEPD to Chinese hamster autosomes 8 and 9: a cytogenetic basis for functional haploidy of an autosomal linkage group in CHO cells.

Concordant segregation analysis of Chinese hamster (Cricetulus griseus) isozymes and chromosomes segregating from interspecific somatic cell hybrids made with mouse C11D cells revealed the locations of GPI and PEPD on chromosome 9 and TPI on chromosome 8 in both euploid Chinese hamster and CHO cells. The patterns of electrophoretically detectable shift mutants of these loci in CHO cells were consistent with the observed presence of two normally banded chromosome 8's and monosomy for chromosome 9. These findings and the isolation of three independent, null PEPD mutants in only 527 ethyl methansulfonate-exposed clones indicate that the high frequency of recovery of recessive drug resistant mutants in CHO cells may be due not only to haploidy caused by deletions and monosomy but also by great sensitivity of certain loci to particular mutagens.

Animals↗
PubMed2006

Rubinstein-Taybi Syndrome: spectrum of CREBBP mutations in Italian patients.

BACKGROUND: Rubinstein-Taybi Syndrome (RSTS, MIM 180849) is a rare congenital disorder characterized by mental and growth retardation, broad and duplicated distal phalanges of thumbs and halluces, facial dysmorphisms and increased risk of tumors. RSTS is caused by chromosomal rearrangements and point mutations in one copy of the CREB-binding protein gene (CREBBP or CBP) in 16p13.3. To date mutations in CREBBP have been reported in 56.6% of RSTS patients and an average figure of 10% has ascribed to deletions. METHODS: Our study is based on the mutation analysis of CREBBP in 31 Italian RSTS patients using segregation analysis of intragenic microsatellites, BAC FISH and direct sequencing of PCR and RT-PCR fragments. RESULTS: We identified a total of five deletions, two of the entire gene and three, all in a mosaic condition, involving either the 5' or the 3' region. By direct sequencing a total of 14 de novo mutations were identified: 10 truncating (5 frameshift and 5 nonsense), one splice site, and three novel missense mutations. Two of the latter affect the HAT domain, while one maps within the conserved nuclear receptor binding of (aa 1-170) and will probably destroy a Nuclear Localization Signal. Identification of the p.Asn1978Ser in the healthy mother of a patient also carrying a de novo frameshift mutation, questions the pathogenetic significance of the missense change reported as recurrent mutation. Thirteen additional polymorphisms, three as of yet unreported, were also detected. CONCLUSION: A high detection rate (61.3%) of mutations is confirmed by this Italian study which also attests one of the highest microdeletion rate (16%) documented so far.

Adolescent↗
PubMed2001

Association and linkage of leprosy phenotypes with HLA class II and tumour necrosis factor genes.

Previous analyses indicate major gene control of susceptibility to leprosy per se and the HLA class II region has been implicated in determining susceptibility and control of clinical phenotype. Segregation analysis using data from 76 Brazilian leprosy multi-case pedigrees (1166 individuals) supported a two locus model as the best fit: a recessive major gene and a recessive modifier gene(s) (single locus vs two locus model, P = 0.0007). Combined segregation and linkage analysis to the major locus, showed strong linkage to HLA class II (HLA-DQB1 P = 0.000002, HLA-DQA1 P = 0.000002, HLA-DRB1 P = 0.0000003) and tumour necrosis factor genes (TNF P = 0.00002, LTA P = 0.003). Extended transmission disequilibrium testing, using multiple affected family members, demonstrated that the common allele TNF*1 of the -308 promoter region polymorphism showed linkage and/or association with disease per se, at a high level of significance (P < 0.0001). Two locus transmission disequilibrium testing suggested susceptibility (TNF*1/LTA*2) and protective (TNF*2/LTA*2) haplotypes in the class iii region. Taken together the segregation and HLA analyses suggest the possibility of more than one susceptibility locus in the MHC.

Brazil↗
PubMed2002

Identification of genetic markers linked to banana streak disease expression in inter-specific Musa hybrids.

Recently-introduced inter-specific Musa hybrids, bred for improved yield and resistance to diseases, have been found to be widely infected with banana streak virus (BSV), the causal agent of banana streak disease (BSD). One hypothesis suggests: (1) that BSD occurrence in these inter-specific hybrids results from activation of BSV-Ol endogenous pararetrovirus sequences (EPRV) integrated into the Musa genome rather than from external sources of infection, and (2) that the process of genetic hybridisation may be one factor involved in triggering episomal expression of the BSV integrants. In order to test this hypothesis we carried out a genetic analysis of BSD incidence in a F1 triploid ( Musa AAB) population produced by inter-specific hybridisation between virus and disease-free diploid Musa balbisiana (BB) and tetraploid Musa acuminata (AAAA) parents. Half of the F1 progeny of this cross expressed BSV particles. Using PCR amplification to determine the presence or absence of BSV-Ol EPRVs, it was determined that this endogenous sequence was specific to the M. babisiana genome and occurred in a homozygous state. Using bulk segregant analysis, ten AFLP markers co-segregating with the absence and/or presence of BSV infection were identified in the M. balbisiana genome, but were absent from the M. acuminata genome. Seven of these markers segregated with the presence of a BSV particle and three with the absence of BSV particles. Analysis of the segregation of these markers using a test-cross configuration allowed the construction of a genetic map of the linkage group containing the locus associated with BSV infection in the F1 hybrid population. These data indicate that a genetic mechanism is involved in BSV appearance, and suggest that a monogenic allelic system confers the role of carrier to the M. balbisiana parent.

Alleles↗
PubMed1993

Segregation and linkage analysis in five manic depression pedigrees excludes the 5HT1a receptor gene (HTR1A).

Five kindreds selected through probands attending an Icelandic hospital were recruited for linkage studies of manic depression. The rates of affection were equal for males and females and the age of onset appeared to be predominantly in early adult life, since prevalence did not rise appreciably with age. A complex segregation analysis was performed using the computer program POINTER to obtain maximum likelihood estimates of the contributions to liability from multifactorial transmission and a single major locus. Likelihood ratios between models supported a role for a single major locus which was dominant and had moderately high penetrance with, in the case of unipolar illness, additional multifactorial transmission. The best-fitting parameters were used to devise a transmission model for linkage analysis. Three markers on chromosome 5 were studied, at D5S76, D5S6 and D5S39. Strongly negative lod scores were obtained which were less than -2 over a distance of 40 cM, which included the region to which the gene for the 5HT1a receptor has been mapped.

Bipolar Disorder↗
PubMed2003

Combined segregation and linkage analysis of fibrinogen variability in Israeli families: evidence for two quantitative-trait loci, one of which is linked to a functional variant (-58G > A) in the promoter of the alpha-fibrinogen gene.

The association of alpha- and beta-fibrinogen polymorphisms with plasma fibrinogen levels was examined in a sample of 452 family members from 80 Israeli kindreds. The measured genotype analysis indicated that the beta-fibrinogen -455G > A polymorphism was not associated with fibrinogen levels, while the alpha-fibrinogen -58G > A locus showed a significant association with fibrinogen levels (chi2= 17.7; df = 3; p < 0.001), with the -58A allele being associated with higher levels. Segregation analysis in this sample suggested a recessive quantitative-trait locus (QTL) with a major effect that controlled the sex- and age-adjusted fibrinogen levels. Results from a combined segregation/linkage analysis indicated that a single QTL influencing plasma fibrinogen is in gametic equilibrium with the beta-fibrinogen -455G > A and alpha-fibrinogen -58G > A polymorphisms. An extended analysis with a two-QTL model significantly improved the fit of the model (p < or = 0.001), and gave support for linkage between the fibrinogen QTL and the alpha-fibrinogen polymorphism. In vitro analysis with a DNA fragment containing this variant, linked to a reporter gene, showed 2-fold higher expression of the A allele compared to the G allele in the liver cell line HepG2, both under basal conditions and after stimulation with interleukin 6. These results demonstrate that two QTLs are jointly involved in determining plasma fibrinogen levels in this sample of families, one of which is located close to a functional variant in the alpha-fibrinogen locus.

Cell Line↗
PubMed1995

How can maximum likelihood methods reveal candidate gene effects on a quantitative trait?

Different maximum likelihood approaches were used to explore the role of candidate genes in the variability of quantitative trait Q1 while accounting for the effects of age, Q2, and Q3. Segregation analysis, under the class D regressive model, provides evidence for a Mendelian gene effect on the adjusted trait Q1. Results of gene mapping through lod-score analyses remain puzzling. Pairwise lod scores indicate a possible linkage with the candidate gene C5 which is excluded when using tightly linked informative marker loci. Finally, our combined segregation and linkage analysis clearly shows that a C5 linked gene is involved in Q1 variability. However, given the lod-score results within the C5 region, we postulate a more complex mechanism for Q1 than a single di-allelic C5 linked gene. The knowledge of the true model (C5 is MG1 and has three alleles) permits a partial explanation of our results. This study demonstrates the advantages of using complementary approaches to reveal the role of candidate genes in complex traits, and the value of simultaneous estimation of linkage and segregation parameters.

Alleles↗
PubMed1995

Marker enrichment and high-resolution map of the segment of potato chromosome VII harbouring the nematode resistance gene Gro1.

The dominant allele Gro1 confers on potato resistance to the root cyst nematode Globodera rostochiensis. The Gro1 locus has been mapped to chromosome VII on the genetic map of potato, using RFLP markers. This makes possible the cloning of Gro1 based on its map position. As part of this strategy we have constructed a high-resolution genetic map of the chromosome segment surrounding Gro1, based on RFLP, RAPD and AFLP markers. RAPD and AFLP markers closely linked to Gro1 were selected by bulked segregant analysis and mapped relative to the Gro1 locus in a segregating population of 1105 plants. Three RFLP and one RAPD marker were found to be inseparable from the Gro1 locus. Two AFLP markers were identified that flanked Gro1 at genetic distances of 0.6 cM and 0.8 cM, respectively. A genetic distance of 1 cM in the Gro1 region corresponds to a physical distance of ca. 100 kb as estimated by long-range restriction analysis. Marker-assisted selection for nematode resistance was accomplished in the course of constructing the high-resolution map. Plants carrying the resistance allele Gro1 could be distinguished from susceptible plants by marker assays based on the polymerase chain reaction (PCR).

Animals↗
PubMed1988

[Preliminary analysis of inheritance of scoliosis].

90 pedigrees (283 individuals) were used for statistical and segregation analysis of scoliosis inheritance. It was shown that inheritance of scoliosis may be described by the monogenic model with incomplete penetrance of heterozygotes, the latter being lower in men than in women. The monogenic model allows to perform correct predictions, the probability of incorrect prediction being about 0.1.

Female↗
PubMed1999

A molecular marker that segregates with sorghum leaf blight resistance in one cross is maternally inherited in another.

Leaf blight-resistant sorghum accession SC326-6 was crossed to the susceptible cultivar BTx623 to analyze the genetic basis for resistance. Field scoring of inoculated F2 progeny revealed that resistance was transmitted as a dominant single-gene trait. By combining the random amplified polymorphic DNA (RAPD) technique with bulked-segregant analysis, it was possible to identify PCR amplification products that segregated with disease response. Primer OPD12 amplified a 323-bp band (D12R) that segregated with resistance. Creation of longer primers, or SCARs (sequence characterized amplified regions) for D12R resulted in the amplification of a single major band of the predicted size from all the resistant F2 progeny and the resistant parent SC326-6, but not from BTx623 or 24 of 29 susceptible F2 progeny. The SCAR primers also amplified a single band with DNA from IS3620C, the female parent in a cross with BTx623 that has been used to produce a recombinant inbred population for RFLP mapping. An equivalent band was amplified from all 137 recombinant inbred progeny, indicating that organelle DNA is the amplification target in this cross.

Base Sequence↗
PubMed1997

Immunogenetics of leishmanial and mycobacterial infections: the Belem Family Study.

In the 1970s and 1980s, analysis of recombinant inbred, congenic and recombinant haplotype mouse strains permitted us to effectively 'scan' the murine genome for genes controlling resistance and susceptibility to leishmanial infections. Five major regions of the genome were implicated in the control of infections caused by different Leishmania species which, because they show conserved synteny with regions of the human genome, immediately provides candidate gene regions for human disease susceptibility genes. A common intramacrophage niche for leishmanial and mycobacterial pathogens, and a similar spectrum of immune response and disease phenotypes, also led to the prediction that the same genes/candidate gene regions might be responsible for genetic susceptibility to mycobacterial infections such as leprosy and tuberculosis. Indeed, one of the murine genes (Nramp1) was identified for its role in controlling a range of intramacrophage pathogens including leishmania, salmonella and mycobacterium infections. In recent studies, multicase family data on visceral leishmaniasis and the mycobacterial diseases, tuberculosis and leprosy, have been collected from north-eastern Brazil and analysed to determine the role of these candidate genes/regions in determining disease susceptibility. Complex segregation analysis provides evidence for one or two major genes controlling susceptibility to tuberculosis in this population. Family-based linkage analyses (combined segregation and linkage analysis; sib-pair analysis), which have the power to detect linkage between marker loci in candidate gene regions and the putative disease susceptibility genes over 10-20 centimorgans, and transmission disequilibrium testing, which detects allelic associations over 1 centimorgan (ca. 1 megabase), have been used to examine the role of four regions in determining disease susceptibility and/or immune response phenotype. Our results demonstrate: (i) the major histocompatibility complex (MHC: H-2 in mouse, HLA in man: mouse chromosome 17/human 6p; candidates class II and class III including TNF alpha/beta genes) shows both linkage to, and allelic association with, leprosy per se, but is only weakly associated with visceral leishmaniasis and shows neither linkage to nor allelic association with tuberculosis; (ii) no evidence for linkage between NRAMP1, the positionally cloned candidate for the murine macrophage resistance gene Ity/Lsh/Bcg (mouse chromosome 1/human 2q35), and susceptibility to tuberculosis or visceral leishmaniasis could be demonstrated in this Brazilian population; (iii) the region of human chromosome 17q (candidates NOS2A, SCYA2-5) homologous with distal mouse chromosome 11, originally identified as carrying the Scl1 gene controlling healing versus nonhealing responses to Leishmania major, is linked to tuberculosis susceptibility; and (iv) the 'T helper 2' cytokine gene cluster (proximal murine chromosome 11/human 5q; candidates IL4, IL5, IL9, IRF1, CD14) controlling later phases of murine L. major infection, is not linked to human disease susceptibility for any of the three infections, but shows linkage to and highly significant allelic association with ability to mount an immune response to mycobacterial antigens. These studies demonstrate that the 'mouse-to-man' strategy, refined by our knowledge of the human immune response to infection, can lead to the identification of important candidate gene regions in man.

Animals↗
PubMed1997

Major histocompatibility complex (MHC) class III genetics in two Amerindian tribes from southern Brazil: the Kaingang and the Guarani.

Population genetic studies of the major histocompatibility complex (MHC) class III region, comprising C2, BF and C4 phenotypes, and molecular genetic data are rarely available for populations other than Caucasoids. We have investigated three Amerindian populations from Southern Brazil: 131 Kaingang from Ivaí (KIV), 111 Kaingang (KRC) and 100 Guarani (GRC) from Rio das Cobras. Extended MHC haplotypes were derived after standard C2, BF, C4 phenotyping and restriction fragment length polymorphism (RFLP) analysis with TaqI, together with HLA data published previously by segregation analysis. C2 and BF frequencies corresponded to other Amerindian populations. C4B*Q0 frequency was high in the GRC (0.429) but low in the Kaingang. Unusual C4 alleles were found, viz. C4A*58, A*55 and C4B*22 (presumably non-Amerindian) and aberrant C4A*3 of Amerindian origin occurring with a frequency of 0.223 in the GRC. C4A*3 bands of homo- and heterozygous individuals carrying this variant were Rodgers 1 positive and Chido 1,3 positive, showed a C4A specific lysis type and a C4A like alpha-chain. Polymerase chain reaction studies and sequencing showed that this is based on a C4A*3 duplication with a regular C4A*3 and a partially converted C4A*0304 carrying the C4B specific epitopes Ch 6 and Ch 1,3. Associations of class III haplotypes with particular RFLP patterns were similar to those reported for Caucasoids. The previously described association between combined C4A and CYP21P deletions and the 6.4 kb TaqI fragment was not seen in these Amerindians. This fragment occurred within a regular two locus gene structure in the Kaingang, representing a "short" gene at C4 locus I. C4 and CYP21 duplications were frequently observed. The distribution of extended MHC haplotypes provides evidence for a close relationship between the KIV and KRC and a larger genetic distance between the two Kaingang groups and the GRC.

Brazil↗
PubMed1981

Restimulation properties of cloned alloactivated lymphocytes: detection of a novel type of HLA-D/DR region determinant and allelic subtypes for HLA-Dw3 using cloned reagents.

Lymphocytes alloactivated by Dw3 homozygous typing cells were cloned by the method of limiting dilution and cultured for prolonged periods using T-cell growth factor and irradiated pooled leukocytes (as feeder cells). Restimulation specificity of two clones functioning as primed lymphocyte typing reagents was investigated in panel and family studies. Cells from one of the clones (12-2) were always specifically stimulated by HLA-Dw3 antigens shared between the original priming cells and the stimulating panel cells. In an informative family KOH, however, cells from this clone seemed to detect a split in the Dw3 cluster. Cells from the other clone (12-8) failed to respond to Dw3 antigens as expressed by the original priming cells or by panel stimulating cells; rather, specificity of restimulation seemed to be associated with the expression of Dw4 antigens. Family segregation analysis did not support this conclusion however, since stimulating products segregated with one of the three Dw3-bearing haplotypes and with none of three Dw4-bearing haplotypes. This suggested that 12-8 cells may be responsive to antigens different from those detected by homozygous typing cells.

Alleles↗