Tight linkage of the gene for spinocerebellar ataxia to D6S89 on the short arm of chromosome 6 in a kindred for which close linkage to both HLA and F13A1 is excluded.

A locus for an autosomal dominant form of spinocerebellar ataxia (SCA1) has been assigned to the short arm of chromosome 6 on the basis of linkage to the major histocompatibility system (HLA). In this study of a five-generation American black family, close linkage between the disease locus and both HLA and the coagulation factor XIIIA (F13A1) locus was excluded, and lod scores for all locations of the disease locus between HLA and F13A1 were less than -1.4. These results suggest that the locus causing spinocerebellar ataxia in this family is not in this region. However, the disease locus was found to be closely linked to a microsatellite polymorphism, D6S89, which is between HLA and F13A1. The maximum lod score for SCA1 and D6S89 is 4.90 at a recombination fraction of 0, both in males and in females. These data show that exclusion of close linkage to the HLA complex and F13A1 in a kindred with spinocerebellar ataxia does not rule out the possibility that the disease locus in that family is on 6p. Accordingly, all families segregating a dominantly inherited ataxia should be evaluated for linkage to D6S89, to determine whether the locus causing the disease is SCA1.     

Analysis for linkage between F13A and three chromosome 6 marker loci: evidence for 6pter: F13A:HLA:GL01:cen gene order

Summary The results of the present study provide independent support for F13A:HLA linkage and refine the F13A: HLA and F13A: GLO1 linkage relationships. Analysis of the corresponding recombination fractions for the total paternal F13A:HLA and F13A:GLO1 peak lod scores() indicates a locus order of 6pter: F13A:HLA:GLO1:cen. Lod scores between F13A and PLG, a locus recently assigned to chromosome 6, exclude close linkage between these loci.     

Linkage between the loci for mitochondrial malic enzyme (ME2) and coagulation factor XIIIA subunit (F13A)

Summary The locus for the mitochondrial malic enzyme (ME2) seems to be closely linked to the gene coding for the A subunit of coagulation factor XIII (F13A). From 18 informative families with 54 children a maximum lod score of 4.33 was obtained at a recombination fraction of 0.10. Since the assignment of F13A to the short arm of chromosome 6 was recently confirmed, the locus for ME2 can be added to this linkage group. The map order seems to be: GLO1-HLA-F13A-ME2.     

Fine Structure and Instability of the Ml-a Locus in Barley

There are many naturally occurring variants at the Ml-a locus in barley that confer resistance to the powdery mildew fungus Erysiphe graminis f. sp. hordei. Since the Ml-a locus is bracketed by Hor-1 and Hor-2, genes that encode storage proteins in the endosperm, the Ml-a locus is amenable to fine structure analysis. Rare susceptible recombinants, as judged by exchange of flanking markers, were recovered in F3 families from the Ml-a10 X Ml-a1, Ml-a1 X Ml-a15 and Ml-a6 X Ml-a13 crosses. Some susceptible recombinants were recovered from the Ml-a6 X Ml-a13 cross that did not fit the expected F3 family segregation ratios. The Ml-a6/Ml-a13 recombinants often reverted to resistance in subsequent generations. No recombinants were recovered in the reciprocal cross, Ml-a13 X Ml-a6. The possibility of a transposable element and a possible linear order of six "alleles" at the Ml-a locus is discussed.     

A structural locus for coagulation factor XIIIA (F13A) is located distal to the HLA region on chromosome 6p in man

Linkage between the locus for coagulation factor XIIIA (F13A) and HLA-region genes has been revealed during a linkage study between F13A and approximately 40 other polymorphic marker genes. In males, the maximum lod score between F13A and HLA-region genes (HLA-A, -C, -B, -DR; C4A, -B; Bf; and/or C2) is 7.60 at theta 1 = .18. To GLO, the maximum lod score is 2.37 at theta 1 = .19; to PGM3, .22 at theta 1 = .35. Female data indicate a clear sex difference in recombination frequency between F13A and HLA. The present findings, in combination with earlier knowledge of PGM3/GLO/HLA localization and gene distances, show that F13A is distal to HLA on the short arm of chromosome 6 in man. It is thus likely that by including FXIIIA typing in linkage studies, the whole male 6p is within mapping distance of highly polymorphic, classical marker genes. Earlier findings that the Hageman factor gene (F12) is located in the same chromosomal region may indicate the presence of a coagulation factor gene cluster in this region.     

Localization of the coagulation factor XIII A subunit gene (F13A) to chromosome bands 6p24----p25

Electrophoretic studies of the genetic variation of the A subunit of coagulation factor XIII (F13A) have shown that the A subunits expressed in placenta and in the circulation are the products of the same gene locus. In situ hybridization studies with a cDNA fragment encoding the amino terminal region of the A subunit have localized the gene to bands p24----p25 on chromosome 6. This confirms previous studies that showed linkage between F13A and the major histocompatibility complex.     

Regional mapping of the gene for autosomal dominant spinocerebellar ataxia (SCA1) by localizing the closely linked D6S89 locus to 6p24.2----p23.05.

The locus for one subtype of autosomal dominant spinocerebellar ataxias (SCA1) is closely linked (within 1-2 cM) to D6S89, which contains a highly polymorphic dinucleotide repeat sequence. D6S89 has been mapped previously to 6p24----p21.3, between the HLA and F13A1 loci. Mutant cell lines were used to correlate the absence or presence of D6S89 with cytogenetically detectable interstitial 6p deletions. The results allowed us to map D6S89 to the 6p24.2----p23.05 region. The close linkage of SCA1 to D6S89 indicates that this locus is most likely located in the 6p24----p23 segment.     

Localization of the autosomal dominant HLA-linked spinocerebellar ataxia (SCA1) locus, in two kindreds, within an 8-cM subregion of chromosome 6p.

Two large kindreds with HLA-linked, autosomal dominant spinocerebellar ataxia (SCA1) were examined with markers from chromosome 6p to determine the location of the SCA1 locus. Results of the three-point analysis between the markers HLA-A, SCA1, and F13A overwhelmingly favor the conclusion that SCA1 is located distal of HLA and proximal of F13A. In addition, our data strongly support the conclusion that SCA1 lies centromeric and genetically very close to the highly informative D6S89 marker within the 8-cM chromosomal segment flanked by the D6S88 and D6S89 markers. In the two kindreds, one recombinant was observed between D6S89 and SCA1, resulting in a recombination fraction of .014 between the two loci.     

Spinocerebellar ataxia: multipoint linkage analysis of genes associated with the disease locus

Summary Spinocerebellar ataxia (SCA) was studied in a seven-generation (Schut-Swier) kindred using linkage analysis to localize further the autosomal dominant, HLA-linked, disease-producing SCA1 locus relative to four other loci that map to the short arm of human chromosome 6. Genotypes for each locus were determined in as many individuals as possible from a total of 162 affected and unaffected family members that were studied. A maximum pairwise lod score of 8.52 ( _m = 0.10, _f = 0.22) for linkage between SCA1 and HLA-A was observed. Multipoint linkage analyses for the SCA1, HLA-A, F13A, D6S7, and GLO1 loci revealed that the SCA1 locus is most probably located telomeric to HLA-A, with a likely location between HLA-A and F13A.     

Recombination of alleles conferring specific resistance to powdery mildew at the Mla locus in barley.

In barley (Hordeum vulgare L.), the Mla locus conditions reaction to the powdery mildew fungus Erysiphe graminis f.sp. hordei. Enrichment for genetic recombinants in the Mla region is possible by screening for recombination events between the flanking endosperm storage proteins hordeins C and B. Reciprocal crosses were made between the Franger (C.I. 16151) and Rupee (C.I. 16155) lines carrying the (Mla6 + Mla14) and Mla13 alleles, respectively. Recombinants were identified from F2 segregants by analyzing the extracted hordein polypeptides by sodium dodecyl sulphate - polyacrylamide gel electrophoresis. Two hundred and seventy-six recombinant gametes were identified from the 1800 seeds that were screened. Recombination of Mla alleles was analyzed by inoculating F4 recombinant lines with three isolates of E. graminis (A27, 5874, and CR3), which recognize specific Mla alleles. The linkage order established is Hor1-Mla6-Mla13-Mla14-Hor2. The genetic distances between Hor1-Mla6, Mla6-Mla13, and Mla13-Hor2, obtained using Mapmaker 3.0b F3 intercross analysis, are 3.9, 0.2, and 5.2 cM, respectively.     

Genetic and physical mapping of xa13, a recessive bacterial blight resistance gene in rice

 The recessive gene, xa13, confers resistance to Philippine race 6 (PXO99) of the bacterial blight pathogen Xanthomonas oryzae pv oryzae. Fine genetic mapping and physical mapping were conducted as initial steps in an effort to isolate the gene. Using nine selected DNA markers and two F₂ populations of 132 and 230 plants, xa13 was fine-mapped to a genomic region <4 cM on the long arm of rice chromosome 8, flanked by two RFLP markers, RG136 and R2027. Four DNA markers, RG136, R2027, S14003, and G1149, in the target region were used to identify bacterial artificial chromosome (BAC) clones potentially harboring the xa13 locus from a rice BAC library. A total of 11 BACs were identified, forming four separate contigs including a single-clone contig, 29I3, associated with the RG136 STS marker, the S14003 contig consisting of four clones (44F8, 41O2, 12A16, and 12F20), the G1149 contig with two clones, 23D11 and 21H18, and the R2027 contig consisting of four overlapping clones, 42C23, 30B5, 6B7 and 21H14. Genetic mapping indicated that the xa13 locus was contained in the R2027 contig. Chromosomal walking on the R2027 contig resulted in two more clones, 33C7 and 14L3. DNA fingerprinting showed that the six clones of the R2027 contig were overlapping. Clone 44F8 hybridized with a single fragment from the clone 14L3, integrating the R2027 and S14003 contigs into a single contig consisting of ten BAC clones with a total size of approximately 330 kb. The physical presence of the xa13 locus in the contig was determined by mapping the ends of the BAC inserts generated by TAIL-PCR. In an F₂ population of 230 plants, the BAC-end markers 42C23R and 6B7F flanked the xa13 locus. The probes 21H14F and 21H14R derived from BAC clone 21H14 were found to flank xa13 at a distance of 0.5 cM on either side, using a second F₂ population of 132 plants. Thus, genetic mapping indicated that the contig and the 96-kb clone, 21H14, contained the xa13 locus. Received: 15 August 1998 / Accepted: 29 September 1998     

Investigation of the porcine MUC13 gene: isolation, expression, polymorphisms and strong association with susceptibility to enterotoxigenic Escherichia coli F4ab/ac

Enterotoxigenic Escherichia coli (ETEC) F4ab and F4ac are major determinants of piglet diarrhoea. The locus for the ETEC F4ab/ac receptor has been mapped to SSC13q41. MUC13 is a transmembrane mucin expressed predominantly in the epithelial surface of the gastrointestinal tract and the MUC13 gene was assigned to SSC13q41, supporting it as a positional candidate gene for the ETEC F4ab/ac receptor. We herein determined the complete 2679-bp cDNA of pig MUC13, and proved that it was most highly expressed in the jejunum and moderately expressed in the trachea, stomach and liver. Furthermore, 13 MUC13 polymorphisms were identified in 19 founder animals of a White Duroc x Erhualian resource population, and a total of 727 F(2) animals with in vitro ETEC F4ab/ac adhesion phenotypes in this population were genotyped for three identified MUC13 polymorphisms including c.576C>T, c.908A>G and c.935A>C. The transmission disequilibrium test showed that the MUC13 alleles and haplotypes were significantly associated with susceptibility/resistance to ETEC F4ab/ac, especially between haplotype [C;G;A] and susceptibility to ETEC F4ac (P = 8.0e-18). Animals inheriting this haplotype were predominantly susceptible to ETEC F4ac (n = 291/303). Moreover, nearly all animals homozygous for haplotype [T;G;C] (n = 39/41) and a majority of those with the [C;A;A]/[T;G;C] haplotype pair (n = 79/88) were resistant to ETEC F4ab. Our results indicated that MUC13 is in strong linkage disequilibrium with the ETEC F4ab/ac receptor locus and provided potential markers for selection of ETEC F4ab/ac-resistant animals in the pig breeding scheme.     

Autosomal dominant ataxia: Genetic evidence for locus heterogeneity from a cuban founder-effect population

The locus for autosomal dominant ataxia with a diagnosis of olivo-ponto-cerebellar atrophy at autopsy has been previously assigned to chromosome 6p. However, evidence for two alternative locations has been reported. We have recently described a large potential founder-effect population of such patients in the Holguin province of Cuba. With an estimated 1,000 patients available for analysis, this extensive cluster of families provides a unique opportunity for the definitive localization of the genetic mutation. Linkage analysis between the disease locus in this population and markers within and flanking the HLA region on chromosome 6 were undertaken in 12 families comprising over 100 affected individuals. Despite similarity in the clinical phenotype between those families where the disease locus has been reported to be linked to the HLA locus and the Cuban patients, no evidence of linkage to this region could be demonstrated in the latter. The disease locus was excluded from a 96-cM genetic interval of the short arm of chromosome 6, encompassing the F13A1-HLA-GLO1-MUT/D6S4 loci. These data strongly support the existence of genetic heterogeneity for the disease.     

Assignment of autosomal dominant spinocerebellar ataxia (SCA1) centromeric to the HLA region on the short arm of chromosome 6, using multilocus linkage analysis.

A 7-generation kindred with the HLA-linked form of spinocerebellar ataxia (SCA1) was studied to determine whether the SCA1 gene maps centromeric or telomeric to the HLA loci. The DNA markers flanking the HLA-(A-B) region were used for polymorphism studies and multilocus linkage analysis. These two markers are the cDNA for the beta-subunit of HLA-DP, which is centromeric to HLA-(A-B), and the cDNA for coagulation factor XIIIa (F13A), which is telomeric to HLA-(A-B). Haplotypes were constructed using multiple polymorphisms for these two DNA markers, and pairwise linkage analysis revealed a maximum lod score of 2.18 for SCA1 versus HLA-DP at a recombination fraction of .05 and a maximum lod score of 0 for SCA1 versus F13A at a recombination fraction of .50. A possible crossover between HLA-(A-B) and HLA-DP was identified, but lack of samples from key individuals hampered the analysis. To clarify the phase and improve the analysis, the two chromosomes 6 for the crossover individual were separated in somatic cell hybrids. The results strongly favored the probability that the crossover occurred between HLA-(A-B-DR) and HLA-DP with SCA1 segregating with HLA-DP, consistent with a location centromeric to HLA-(A-B). Multilocus linkage analysis was used to evaluate further the location of SCA1 relative to F13A, HLA-(A-B), and HLA-DP; the results indicated that the SCA1 gene locus is centromeric to HLA-DP with odds of 46:1 favoring this most likely location over the second most likely location, i.e., telomeric to HLA-(A-B) between the HLA complex and F13A.     

Differential role of three major New Zealand Black-derived loci linked with Yaa-induced murine lupus nephritis

By assessing the development of Y-linked autoimmune acceleration (Yaa) gene-induced systemic lupus erythematosus in C57BL/6 (B6) x (New Zealand Black (NZB) x B6.Yaa)F(1) backcross male mice, we mapped three major susceptibility loci derived from the NZB strain. These three quantitative trait loci (QTL) on NZB chromosomes 1, 7, and 13 differentially regulated three different autoimmune traits: anti-nuclear autoantibody production, gp70-anti-gp70 immune complex (gp70 IC) formation, and glomerulonephritis. Contributions to the disease traits were further confirmed by generating and analyzing three different B6.Yaa congenic mice, each carrying one individual NZB QTL. The chromosome 1 locus that overlapped with the previously identified Nba2 (NZB autoimmunity 2) locus regulated all three traits. A newly identified chromosome 7 locus, designated Nba5, selectively promoted anti-gp70 autoantibody production, hence the formation of gp70 IC and glomerulonephritis. B6.Yaa mice bearing the NZB chromosome 13 locus displayed increased serum gp70 production, but not gp70 IC formation and glomerulonephritis. This locus, called Sgp3 (serum gp70 production 3), selectively regulated the production of serum gp70, thereby contributing to the formation of nephritogenic gp70 IC and glomerulonephritis, in combination with Nba2 and Nba5 in NZB mice. Among these three loci, a major role of Nba2 was demonstrated, because B6.Yaa Nba2 congenic male mice developed the most severe disease. Finally, our analysis revealed the presence in B6 mice of an H2-linked QTL, which regulated autoantibody production. This locus had no apparent individual effect, but most likely modulated disease severity through interaction with NZB-derived susceptibility loci.     

Variability of the F13B locus in South American populations

A population study for the F13B locus was carried out in a total of 396 South American individuals. The analysis comprised new data from 5 Amerindian populations, existing data from 3 Amerindian populations, and I urban sample from La Plata, Argentina. In both pooled Amerindian and La Plata samples, 6 alleles were found. The individual Amerindian samples showed a lower number of alleles, changes in modal alleles, and restricted variability. Interpopulation comparisons revealed significant differences among samples from distinct geographical regions. Differences among the groups were also corroborated by the F(ST) statistic. Data support the hypothesis that genetic drift and gene flow influence Amerindian differentiation.     

Isolation of a polymorphic genomic clone from chromosome 7

Summary A peptide prepared from purified factor 13B (F13B) was sequenced, and a single, long oligonucleotide corresponding to its cognate DNA sequence was constructed and used to screen a chromosome 7 specific genomic library. The positive clone isolated, designated pKV13, was only related to F13B at the oligonucleotide region, but has proved to be a valuable chromosome 7 marker. pKV13 maps to 7pter-q22 in hybrid cell lines, and is present in a chromosome-mediated gene transfer (CMGT) cell line that also contains met and other 7q probes. pKV13 defines a common MspI restriction fragment length polymorphism (RFLP), and is genetically linked to two markers on the long arm of chromosome 7, B79a and COL1A2, both themselves linked to the cystic fibrosis locus. Multipoint linkage analysis demonstrates that KV13 maps centromeric to both B79a and COLIA2. pKV13 has been used to demonstrate the existence of rearrangements within CMGT hybrisd, and will also prove valuable in multipoint linkage studies of other 7q markers. Finally, pKV13 provides a new polymorphic locus for the characterisation of 7q deletions in myeloid disorders such as myelodysplastic syndrome.     

Cytogenetic Definition and Morphogenetic Analysis of Delta, a Gene Affecting Neurogenesis in Drosophila Melanogaster

We have conducted a genetic analysis of a small interval of the third chromosome known to include Delta (Dl), a locus that affects the segregation of the ectoderm into neural and epidermal lineages during embryogenesis and the morphogenesis of some ectodermally derived structures, in Drosophila melanogaster. This analysis has led to the definition of seven independent complementation groups, one of which is Delta, within the interval extending from 91F6-13 to 92A2. Among the extant mutations in these seven loci, only mutations in Dl lead to the so-called neurogenic phenotype: hypertrophy of the nervous system and reduction of the epidermis. Combined cytogenetic and genetic analyses allow us to define absolute proximal (91F5-92A1) and distal (92A2) cytogenetic limits for the Dl locus. We have isolated hypomorphic and amorphic alleles of Dl and find that, for any given allele, there is an inverse correlation between neural hypertrophy and epidermal reduction in embryos and a direct correlation between the severity of embryonic phenotypes in mutant homozygotes and hemizygotes and the imaginal phenotype in heterozygous adults.     

不同生长环境下水稻最上节间长度QTL定位研究

利用由98 个家系组成的 Nipponbare/Kasalath//Nipponbare 回交重组自交系(backcross inbred lines, BIL)作图群体(BC1F12和BC1F13)和复合区间作图方法(CIM), 在3种不同的生长环境下对水稻最上节间长度进行了 QTL 分析。结果表明, 3种不同的生长环境共检测到 13 个 QTL , 分布于第 1, 2, 3, 5, 6, 8, 10, 11 染色体上, 解释性状变异的 3.97%～15.21%。其中qUIL-6在3种不同生长环境中均检测到, qUIL-1a, qUIL-3a, qUIL-3b和 qUIL-10a 等4个位点在两种不同生长环境中均被检测到, 说明这些 QTL 位点受环境影响较小, 表达较为稳定。