Integration of the Physical and Genetic Linkage Map for Human Chromosome 13

We have used a panel of somatic cell hybrids containing different rearrangements of human chromosome 13 to integrate genetic and physical maps of this chromosome. The positions of 17 translocation/deletion breakpoints on human chromosome 13 have been determined relative to the microsatellite markers on the genetic linkage map compiled by Généthon. Because markers on maps from several other Consortium groups have also been analyzed using many of the same hybrids, it was possible to relate these with the Généthon map. The position of all of the chromosome breakpoints have been placed, wherever possible, between two adjacent markers on the genetic linkage maps using PCR analysis for the presence/absence of the markers in the somatic cell hybrids. The positions of the breakpoints have already been determined cytogenetically, and some of these breakpoints are located at landmark positions on the chromosome. The relative density of markers along the chromosome differs between independently derived maps, and, based on the known locations of certain breakpoints in the physical map, inconsistencies in the genetic maps have been identified.     

A Sequence-Tagged Site Map of Human Chromosome 11

We report the construction of 370 sequence-tagged sites (STSs) that are detectable by PCR amplification under sets of standardized conditions and that have been regionally mapped to human chromosome 11. DNA sequences were determined by sequencing directly from cosmid templates using primers complementary to T3 and T7 promoters present in the cloning vector. Oligonucleotide PCR primers were predicted by computer and tested using a battery of genomic DNAs. Cosmids were regionally localized on chromosome 11 by using fluorescence in situ hybridization or by analyzing a somatic cell hybrid panel. Additional STSs corresponding to known genes and markers on chromosome 11 were also produced under the same series of standardized conditions. The resulting STSs provide uniform coverage of chromosome 11 with an average spacing of 340 kb. The DNA sequence determined for use in STS production corresponds to about 0.1% (116 kb) of chromosome 11 and has been analyzed for the presence of repetitive sequences, similarities to known genes and motifs, and possible exons. Computer analysis of this sequence has identified and therefore mapped at least eight new genes on chromosome 11.     

A Primary Genetic Linkage Map of 14 Polymorphic Loci for the Short Arm of Human Chromosome 8

A genetic linkage map of markers for the short arm of human chromosome 8 has been constructed with 14 polymorphic DNA markers on the basis of genotypes obtained in 40 CEPH reference families. This unbroken map spans 45 cM in males and 79 cM in females. The 14 markers include three genes, MSR, LPL, and NEFL, and one anonymous DNA segment that were previously assigned to chromosome 8. The other 10 marker had been isolated from a chromosome 8-specific cosmid library and physically localized to chromosomal bands by fluorescence in situ hybridization. The order of loci determined by genetic linkage was consistent with their physical locations. This map will facilitate efficient linkage studies of human genetic diseases that may be segregating on chromosome 8p and will provide anchor points for development of high-resolution maps for this chromosomal region.     

A Comprehensive Genetic Map of Murine Chromosome 11 Reveals Extensive Linkage Conservation between Mouse and Human

Interspecific backcross animals from a cross between C57BL/6J and Mus spretus mice were used to generate a comprehensive linkage map of mouse chromosome 11. The relative map positions of genes previously assigned to mouse chromosome 11 by somatic cell hybrid or genetic backcross analysis were determined (Erbb, Rel, 11-3, Csfgm, Trp53-1, Evi-2, Erba, Erbb-2, Csfg, Myhs, Cola-1, Myla, Hox-2 and Pkca). We also analyzed genes that we suspected would map to chromosome 11 by virtue of their location in human chromosomes and the known linkage homologies that exist between murine chromosome 11 and human chromosomes (Mpo, Ngfr, Pdgfr and Fms). Two of the latter genes, Mpo and Ngfr, mapped to mouse chromosome 11. Both genes also mapped to human chromosome 17, extending the degree of linkage conservation observed between human chromosome 17 and mouse chromosome 11. Pdgfr and Fms, which are closely linked to II-3 and Csfgm in humans on chromosome 5, mapped to mouse chromosome 18 rather than mouse chromosome 11, thereby defining yet another conserved linkage group between human and mouse chromosomes. The mouse chromosome 11 linkage map generated in these studies substantially extends the framework for identifying homologous genes in the mouse that are involved in human disease, for elucidating the genes responsible for several mouse mutations, and for gaining insights into chromosome evolution and genome organization.     

利用染色体涂染方法建立人和白眉长臂猿(Hylobates hoolock)的比较染色体图谱

除人Y染色体外,本文采用生物素标记的人全部整条染色体特异探针与白眉长臂猿(Hylobates hoolock)有丝分裂中期分裂相进行染色体原位杂交即染色体涂染法以研究人和白眉长臂猿染色体之间的同源性。在白眉长臂猿18对常染色体上检测出了与人22对常染色体同源的59对染色体片段,确定了人和白眉长臂猿之间的精度较高的染色体连锁群。结果表明:自人与白眉长臂猿的祖先分歧以来,大量的染色体间重排(至少发生了39次易位)和染色体内的重排导致了二者核型的差异。根据杂交结果绘制了首份人和白眉长臂猿比较染色体图谱,并结合已有的人和白掌长臂猿(Hylobates lar)(2n=44)和合趾长臂猿(Hylobates syndactylus)(2n=50)的比较染色体图谱对长臂猿属的染色体进化作了初步的探讨。     

Dinucleotide Repeat Loci Contribute Highly Informative Genetic Markers to the Human Chromosome 2 Linkage Map

Microsatellite repeat loci can provide informative markers for genetic linkage. Currently, the human chromosome 2 genetic linkage map has very few highly polymorphic markers. Being such a large chromosome, it will require a large number of informative markers for the dense coverage desired to allow disease genes to be mapped quickly and accurately. Dinucleotide repeat loci from two anonymous chromosome 2 genomic DNA clones were sequenced so that oligonucleotide primers could be designed for amplifying each locus using the polymerase chain reaction (PCR). Five sets of PCR primers were also generated from nucleotide sequences in the GenBank Database of chromosome 2 genes containing dinucleotide repeats. In addition, one PCR primer pair was made that amplifies a restriction fragment length polymorphism on the TNP1 gene (Hoth and Engel, 1991). These markers were placed on the CEPH genetic linkage map by screening the CEPH reference DNA panel with each primer set, combining these data with those of other markers previously placed on the map, and analyzing the combined data set using CRI-MAP and LINKAGE. The microsatellite loci are highly informative markers and the TNP1 locus, as expected, is only moderately informative. A map was constructed with 38 ordered loci (odds 1000:1) spanning 296 cM (male) and 476 cM (female) of chromosome 2 compared with 306 cM (male) and 529 cM (female) for a previous map of 20 markers.     

A High-Resolution Genetic Map of the Nervous Locus on Mouse Chromosome 8

The nervous (nr) mutant mouse displays two gross recessive traits: both an exaggeration of juvenile hyperactivity and a pronounced ataxia become apparent during the third and fourth postnatal weeks. Using an intersubspecific intercross, we have established a high-resolution map of a segment of mouse Chromosome 8 that places thenrlocus in a genomic segment defined byD8Rck1on the centromeric end andD8Mit3on the telomeric end. This map position places thenrlocus within the BALB/cGr congenic region of the C3HeB/FeJ-nrstrain, confirming the accuracy of our study. We used this map position to identify and evaluate three genes—ankyrin 1, cortexin, and farnesyltransferase—as candidates for thenrgene. These three genes were eliminated from consideration but allowed us to establish the conservation of synteny between the region containing thenrlocus and a segment of the short arm of human chromosome 8 (8p21–p11.2). Finally, the incomplete penetrance of thenrphenotype led us to perform a screen for modifier loci, and we present evidence that such a nervous modifier locus may exist on mouse Chromosome 5.     

Physical and Genetic Map of the Pasteurella multocida A:1 Chromosome

A physical and genetic map of the Pasteurella multocida A:1 genome was generated by using the restriction enzymes ApaI, CeuI, and NotI. The positions of 23 restriction sites and 32 genes, including 5 rrn operons, were localized on the 2.35-Mbp single circular chromosome. This report presents the first genetic and physical map for this genus.     

9号染色体10个STR基因座的遗传制图

运用小规模实验初步探讨了以中国人群为基础的遗传图绘制工作的必要性。18个无关汉族3代家系共131份血样采自甘肃省白银地区,常规PCR扩增9号染色体的10个STR基因座,采用非变性聚丙烯酰凝胶电泳分析。PCR产物经克隆测序确定核心序列重复次数,采用标准命名法命名各等位基因,用POPGENE软件包计算各基因座等位基因频率,并进行Hardy-Weiberg平衡检验,用Linkage软件包进行各基因座之间连锁关系分析。根据连锁分析结果绘制了中国人群由10个STR基因座构成的9号染色体遗传图。基于中国人群体的9号染色体10个STR连分析锁分析结果与GDB检索结果之间存在较显著的差异,这种差异同时表现在个别基因座之间和0号染色体遗传图总长度上。男、女遗传结果之间在较显著的差异,这种差异同时表现在个别基因之间和9号染色体总长度上。男、女遗传图总长度为129．21cM和178．4cM,均大高加索入。说明了在运用GDB数据之前,有必要根据实验群体进行基因座的初步评估,并且有必要对基于中国人群体的遗传图进行进一步的研究。     

A Radiation Hybrid Map of 95 STSs Spanning Human Chromosome 13q

We have constructed a high-resolution physical map of the long arm of human chromosome 13 using a panel of 94 radiation hybrids. A comprehensive map of 95 chromosome 13-specific sequence tagged sites (STSs) spanning 13q from the presumed centromere at D13Z1 to the known telomere was obtained by multipoint maximum likelihood statistical methods. The 95 markers have an average retention frequency of 10%, with markers closer to the centromere having much greater retention frequencies (22-49%) than distal 13q markers (2-12%) The most likely radiation hybrid map localized the 95 STSs into 54 unique map positions, 34 with odds of 1000:1 or greater; the comprehensive map localized all but 17 STSs with odds exceeding 10:1. The total map length of 13q was 1302 cR₉₀₀₀ (range 6.4-94.4 cR₉₀₀₀) and a physical distance of 98 Mb, so that 1% breakage in the RH panel corresponds to 75 kb. A comparison of the comprehensive RH map to genetic maps of chromosome 13q shows identical locus orders for the common markers, with two exceptions over 1-cM distances. We discuss the possible relationships between the genetic and the radiation hybrid maps.     

猪3号染色体九个微卫星位点的遗传多态性研究和遗传图谱构建

从已公布的猪 3号染色体连锁图谱中选取 9个微卫星位点 ,分析了这些位点在大白猪×梅山猪资源家系F2代 140头个体上的多态性 ,利用Crimap软件分别构建了猪 3号染色体两性平均连锁图谱以及公、母畜连锁图谱。结果表明 :各位点等位基因数为 2～ 4个 ,杂合度为 0 .436～ 0 .6 5 6 ,多态信息含量为 0 .35 1～ 0 .5 82 ;本研究所构建的平均连锁图谱全长为 16 1.1cM ,公、母畜连锁图谱全长分别为 135 .8cM和 188.7cM。与USDA所公布的连锁图谱相比 ,两者的标记顺序一致 ,但我们的图谱标记间隔偏大。     

A Genetic Linkage Map for Cattle

We report the most extensive physically anchored linkage map for cattle produced to date. Three-hundred thirteen genetic markers ordered in 30 linkage groups, anchored to 24 autosomal chromosomes (n = 29), the X and Y chromosomes, four unanchored syntenic groups and two unassigned linkage groups spanning 2464 cM of the bovine genome are summarized. The map also assigns 19 type I loci to specific chromosomes and/or syntenic groups and four cosmid clones containing informative microsatellites to chromosomes 13, 25 and 29 anchoring syntenic groups U11, U7 and U8, respectively. This map provides the skeletal framework prerequisite to development of a comprehensive genetic map for cattle and analysis of economic trait loci (ETL).     

Rearrangement of the Genetic Map of Chromosome VII of SACCHAROMYCES CEREVISIAE

The genetic map of the right arm of chromosome VII of Saccharomyces cerevisiae includes markers on a distal segment for which meiotic linkage to the centromere-proximal marker cly8 has not previously been demonstrated. According to the currently accepted map, SUF4 is the most distal marker on the right arm. We have shown by tetrad analysis that SUF4 is linked to cly8 and ade6. The genetic distance between SUF4 and cly8 is 29 cM. These data indicate that the genetic map of the right arm of chromosome VII should be revised by inverting the orientation of the distal segment so that SUF4 is located near cly8, and SUC1 and MAL1 are the most distal markers. With this revision, all of the polymeric fermentation markers that have been mapped are located at the ends of chromosomes.     

A High-Resolution Interval Map of the q21 Region of the Human X Chromosome

In a previous study, we have developed a panel of chromosomal rearrangements for the physical mapping of the q13-q21 region of the human X chromosome (Philippe et al., Genomics 17: 147-152, 1993). Here, we report the physical localization of 36 additional polymorphic markers by polymerase chain reaction analysis. The high density of chromosomal breakpoints in Xq21 allows us to map 58 DNA loci in 22 intervals. As a result, this segment of the X chromosome is saturated with approximately three sequence tagged sites per megabase of DNA, which will facilitate the construction of a YAC contig of this region.     

Genetic Map of Bacteriophage T3

About 200 amber mutants of phage T3 were found to lie in 14 different genes. These genes are homologous to known T7 genes. The genetic map of T3 is very similar to that of T7.     

Combined Physical and Genetic Map of the Pseudomonas putida KT2440 Chromosome

A combined physical and genetic map of the Pseudomonas putida KT2440 genome was constructed from data obtained by pulsed-field gel electrophoresis techniques (PFGE) and Southern hybridization. Circular genome size was estimated at 6.0 Mb by adding the sizes of 19 SwaI, 9 PmeI, 6 PacI, and 6 I-CeuI fragments. A complete physical map was achieved by combining the results of (i) analysis of PFGE of the DNA fragments resulting from digestion of the whole genome with PmeI, SwaI, I-CeuI, and PacI as well as double digestion with combinations of these enzymes and (ii) Southern hybridization analysis of the whole wild-type genome digested with different enzymes and hybridized against a series of probes obtained as cloned genes from different pseudomonads of rRNA group I and Escherichia coli, as P. putida DNA obtained by PCR amplification based on sequences deposited at the GenBank database, and by labeling of macrorestriction fragments of the P. putida genome eluted from agarose gels. As an alternative, 10 random mini-Tn5-Km mutants of P. putida KT2440 were used as a source of DNA, and the band carrying the mini-Tn5 in each mutant was identified after PFGE of a series of complete chromosomal digestions and hybridization with the kanamycin resistance gene of the mini-Tn5 as a probe. We established a circular genome map with an average resolution of 160 kb. Among the 63 genes located on the genetic map were key markers such as oriC, 6 rrn loci (rnnA to -F), recA, ftsZ, rpoS, rpoD, rpoN, and gyrB; auxotrophic markers; and catabolic genes for the metabolism of aromatic compounds. The genetic map of P. putida KT2440 was compared to those of Pseudomonas aeruginosa PAO1 and Pseudomonas fluorescens SBW25. The chromosomal backbone revealed some similarity in gene clustering among the three pseudomonads but differences in physical organization, probably as a result of intraspecific rearrangements.     

A Radiation Hybrid Map of Mouse Chromosome 13

A mouse radiation hybrid (RH) panel was used to make a framework map for the entire length of mouse chromosome (Chr) 13. Forty-one loci were typed, and while most used primers flanking simple sequence repeats, some genes were included. The most proximal and distal loci are D13Mit132 and D13Mit35. The estimate of map length for Chr 13 is 1328 cR. The map is compared with the same set of loci from the consensus map for Chr 13, which is 70 cM in length, and also with a recombinational map derived from an intraspecies cross typed for many of the same loci. The mouse RH panel gave good resolution for Chr 13 and at the distal end allowed separation of previously nonrecombinant markers that are present on a single 620-kb YAC clone. Data analysis was performed using the RH option for Map Manager QT. This framework RH map of Chr 13 is the second of a series of RH maps for mouse chromosomes.     

A Genetic Analysis of the Werner Syndrome Region on Human Chromosome 8p

Werner syndrome (WRN) is an inherited disorder that produces symptoms of premature aging. This disease is caused by a recessive mutation that has previously been mapped to chromosome 8p. We have now used genetic linkage analysis to map the WRN gene relative to chromosome 6 reference loci, to screen candidate genes, and to identify a novel dinucleotide repeat polymorphic marker closely linked to WRN. The WRN locus was mapped relative to the marker loci, PLAT, ANK1, D8S135, and D8S87 of the comprehensive chromosome 8 linkage map. The heregulin (HRG) and the fibroblast growth factor receptor 1 genes (FGFR1) have been mapped to chromosome 8p and are involved in cellular growth. Recombination events were detected between WRN and the HRG and FGFR1 genes, excluding them as candidates for the WRN gene. A polymorphic marker generated in this study, WT251, is linked to WRN at a recombination fraction of 0.006, with a lod score of 16.5.