Linkage of human keratin genes

Two families of keratins, type I and type II, can be distinguished within the intermediate filament family of proteins, and at least 20 genes in the human genome code for the 20 known keratin proteins. In epithelial intermediate filaments, keratins from both families appear to be coordinately expressed. We have screened a library of human genomic DNA and have identified several cases of linkage among homologous and heterologous pairs of keratin genes. Genes coding for type I keratins were found linked to those coding for type II keratins. Linkage was discovered also among homologous genes coding for type I keratins and among genes encoding type II keratins. In addition, we found genes coding for glycine-rich keratins linked to genes coding for those that do not contain glycine-rich regions. Our results raise the possibility that all keratin genes are linked in a single region of the human genome.     

Linkage of ribosomal RNA genes in Leptospira

We determined the linkage of 16S, 23S, and 5S rRNA genes in several strains of Leptospira and Leptonema by DNA-DNA hybridization. Almost all the hybridizations in all leptospires used in these experiments gave two radioactive bands and the results strongly suggest that the number of the 16S and the 23S rRNA genes in those strains is two, respectively. In contrast with the larger rRNAs, the number of 5S rRNA gene was different. In the strains of leptospires, L. biflexa, which were non-parasitic, there are two genes for 5S rRNA, whereas only one gene for 5S rRNA is carried in L. interrogans, which were originally isolated as parasitic. Southern hybridization experiments suggest that those rRNA genes are interspersed on the leptospiral chromosome.     

Linkage disequilibrium in domestic sheep

The last decade has seen a dramatic increase in the number of livestock QTL mapping studies. The next challenge awaiting livestock geneticists is to determine the actual genes responsible for variation of economically important traits. With the advent of high density single nucleotide polymorphism (SNP) maps, it may be possible to fine map genes by exploiting linkage disequilibrium between genes of interest and adjacent markers. However, the extent of linkage disequilibrium (LD) is generally unknown for livestock populations. In this article microsatellite genotype data are used to assess the extent of LD in two populations of domestic sheep. High levels of LD were found to extend for tens of centimorgans and declined as a function of marker distance. However, LD was also frequently observed between unlinked markers. The prospects for LD mapping in livestock appear encouraging provided that type I error can be minimized. Properties of the multiallelic LD coefficient D' were also explored. D' was found to be significantly related to marker heterozygosity, although the relationship did not appear to unduly influence the overall conclusions. Of potentially greater concern was the observation that D' may be skewed when rare alleles are present. It is recommended that the statistical significance of LD is used in conjunction with coefficients such as D' to determine the true extent of LD.     

Maternal-Effect Lethal Mutations on Linkage Group II of Caenorhabditis Elegans

We have analyzed a set of linkage group (LG) II maternal-effect lethal mutations in Caenorhabditis elegans isolated by a new screening procedure. Screens of 12,455 F1 progeny from mutagenized adults resulted in the recovery of 54 maternal-effect lethal mutations identifying 29 genes. Of the 54 mutations, 39 are strict maternal-effect mutations defining 17 genes. These 17 genes fall into two classes distinguished by frequency of mutation to strict maternal-effect lethality. The smaller class, comprised of four genes, mutated to strict maternal-effect lethality at a frequency close to 5 X 10(-4), a rate typical of essential genes in C. elegans. Two of these genes are expressed during oogenesis and required exclusively for embryogenesis (pure maternal genes), one appears to be required specifically for meiosis, and the fourth has a more complex pattern of expression. The other 13 genes were represented by only one or two strict maternal alleles each. Two of these are identical genes previously identified by nonmaternal embryonic lethal mutations. We interpret our results to mean that although many C. elegans genes can mutate to strict maternal-effect lethality, most genes mutate to that phenotype rarely. Pure maternal genes, however, are among a smaller class of genes that mutate to maternal-effect lethality at typical rates. If our interpretation is correct, we are near saturation for pure maternal genes in the region of LG II balanced by mnC1. We conclude that the number of pure maternal genes in C. elegans is small, being probably not much higher than 12.     

Linkage of TNF genes to the HLA-B locus

Pulsed field gel electrophoresis was used to determine the location of the tumour necrosis factor (TNF) alpha and beta genes. They were shown to be linked to the HLA-B locus; analogous to their location in mouse, between the complement (class III) region and H-2D. However, the distance between the TNF genes and the class I region was much greater in man, namely about 260 kb, compared to 70 kb in the mouse. This finding may have implications for some HLA associated diseases.     

Linkage mapping of genes controlling endosperm storage proteins in wheat

Summary A translocation mapping procedure was used to map gene-centromere distances for the genes controlling endosperm proteins on the short arm of each of the chromosomes 1A, 1B and 1D in wheat. The genes controlling triplet proteins (tentatively designated Tri-1) were found to be closely linked to the centromere on chromosome arms 1AS and 1DS and loosely linked to the gliadin genes (Gli-1) on the same arms. The Gli-1 genes segregated independently or were very loosely linked to their respective centromeres. The Gli-B1-centromere map distance on 1BS was also estimated using conventional telocentric mapping and the result was similar to that obtained with the translocation mapping. A simple two-step one-dimensional electrophoretic procedure is described which allows the low-molecular-weight (LMW) glutenin subunits to be separated from the gliadin bands, thus facilitating the genetic analysis of these LMW subunits. No recombination was observed between the genes (designated Glu-3) controlling some major LMW glutenin subunits and those controlling gliadins on chromosome arms 1AS and 1DS. However, in a separate experiment, the genes controlling LMW glutenin subunits on 1BS (Glu-B3) showed a low frequency of recombination with the gliadin genes.Portion of the Ph.D. thesis submitted by the senior author     

Linkage relationships among stress-induced genes in wheat

Linkage relationships among genes responding to water-deficit, salt stress, and heat shock were investigated in diploid wheat, Triticum monococcum L. The position of these gene loci relative to closely linked markers and the centromeres is reported. It is proposed to continue to use the present T. monococcum mapping population and the genetic maps based thereon as a framework for future determination of relationships among other genes related to environmental stress in the tribe Triticeae.     

Linkage mapping of osmotic stress induced genes of oak

Water stress affecting long-lived trees is an important challenge in forestry. Due to global climate change, forest trees will be threatened by extreme conditions like flooding or drought. It is necessary to understand differences in stress tolerance within certain species and to investigate putative relations on genomic level. In this study, osmotic stress induced genes of Quercus ssp. were positioned on two genetic linkage maps of oak. An intra-specific cross 3P*A4 of Quercus robur consisting of 88 offspring and an inter-specific cross 11P*QS29 of Q. robur and Q. petraea comprising 72 full-sibs were analyzed for the inheritance of 14 loci represented by 34 individual single nucleotide polymorphisms. Seven genes in the intra-cross, as well as other six genes in the inter-cross could be mapped and one gene could not be localised due to the severe distortion of the segregation. The collection of expressed sequences involved ribosomal proteins, members of the oxylase/oxygenase gene family, betaine aldehyde dehydrogenase, Dc3 promoter-binding factor, a putative member of the nodulin family, glutathione-S-transferase and proteins with unknown functions. In the inter-cross, two linked markers exhibited 89% deficiency of heterozygosity. Thirteen genes were positioned on ten different oak chromosomes and can serve as orthologous markers in comparative mapping studies within Fagaceae.     

陆地棉枯萎病抗性基因的等位性测定及连锁分析

1995-1996年,对我国育成的有代表性的5个抗病品种进行抗枯萎病基因的等位性测定。结果表明:在所选用的5个抗病品种中至少存在两个不同的抗病基因(暂定名为Fwl和Fw2)。连锁分析显示:Fwl与T586的8个标志性状间、Fw2与T582、T586的13个标志性状间无连锁关系。 Abstract:Allelism in vestigation of genes resistante to Fusarium wilt in cotton suggested that there were 2 genes(assigned symbols Fw1 and Fw2)in 5 cultivars used.No linkage was found between Fw1 and the marker genes in T586 and between Fw2 and those marker genes in T582 and T586.     

Linkage of soybean cyst nematode alleles for incompatibility with soybean

Selection and inbreeding of soybean cyst nematodes increased populations' ability to produce cysts on some soybean lines with concurrent decreases in numbers of cysts on other soybean lines: evidence that some alleles for incompatibility were either linked or at the same loci. Some responses could be explained only by linkage of nematode genes for avirulence. Linkage of nematode alleles for incompatibility could be involved when selection increased numbers of cysts on several lines even though the usual interpretation has been that the lines had some of the same genes for resistance. Most of the lines used in this study may have fewer alleles for incompatibility than most "resistant" lines. Use of these lines with fewer genes for resistance should help in the identification of individual alleles for incompatibility necessary for resolving the allelism and/or linkage of these nematode genes.     

周期节律与肿瘤关系的分子机理

周期节律是由内在时钟系统介导的多重生物过程的周期循环.周期节律系统是由位于大脑的视神经交叉上核的中央时钟系统和位于外周的几乎存在于所有细胞的外周时钟系统组成的.中央时钟与外周时钟都能够对生物体的生理过程进行调控,如激素的分泌、能量代谢、细胞增殖、DNA损伤修复等.而周期节律基因的表达失调,对其下游靶基因包括细胞周期相关基因的表达,以及细胞抗凋亡能力等产生重要的影响.而这一结果会导致细胞增殖加速及基因组不稳定,并可能促进肿瘤的发生.许多实验证据表明,肿瘤是一种节律相关的生理失调,在许多肿瘤中都发现周期节律遭到破坏,如乳腺癌、前列腺癌、子宫内膜癌等.本文将从周期节律对细胞周期进程及对细胞DNA损伤修复的影响来讨论分子水平上细胞的周期节律与肿瘤发生发展的关系.     

Linkage map of Pseudomonas aeruginosa PAT.

The locations of new markers relative to markers previously mapped on the chromosome of Pseudomonas aeruginosa strain PAT were defined by generalized transduction with phage F116L and F1083. Although the marker orders of the various marker groups were deduced mainly from the results of two-factor crosses, the locations of a number of markers were confirmed by three-factor crosses. A linkage map of the chromosome of P. aeruginosa PAT was constructed which shows the relative locations of 50 genes. From the available data, the linkage maps of P. aeruginosa strains PAO and PAT appear to be similar.     

Linkage arrangement of human placental lactogen and growth hormone genes

Human placental lactogen (hPL) and growth hormone (hGH) are two hormones thought to have evolved from a common ancestral gene (along with prolactin), yet they have quite different functions and specificities. The nucleic acid sequences of the respective cDNAs of the two genes share considerable homology, as well as the existence of multiple forms of each gene within the genome. In this study we report on the linkage arrangement of several genes from this group. Two hPL-like genes as well as an hGH gene are shown to be linked within a 38-kilobase pair region of DNA. Linkage between a variant hGH gene and an hPL gene is also shown. The orientation and structural organization of these genes was previously established using 5'- and 3'-specific probes from a placental lactogen cDNA clone and detailed restriction endonuclease mapping. Restriction fragments from the overlapping clones were verified by comparison to digests of high molecular weight genomic DNA. In addition, the location of a specific class of repetitive DNA sequences, the Alu family, was mapped on these clones using the recombinant clone BLUR 8. All members of this multigene family have Alu repeat sequences either immediately flanking their 3' or 5' untranslated regions or within their intervening sequences.     

Linkage and Segregation of Unselected Markers in Matings of Nocardia erythropolis with Nocardia canicruria

The segregation of unselected genes expressing resistance or susceptibility to acriflavine, erythromycin, streptomycin, and tetracycline was analyzed in selected prototrophic recombinants resulting from matings of Nocardia erythropolis and N. canicruria. The organisms were shown to be functionally haploid and appeared to contain not more than one genome. It was postulated that all observed genes were present in a linear linkage group. The ordering of the genes in N. erythropolis was: tetB10 eryB9 his-3 purA1 acr-2 strA1 (respectively, resistance to tetracycline and erythromycin, deficiency for histidine and for purine, and resistance to acriflavine and streptomycin). The ordering of the genes in N. canicruria was: purB2 tetA9 eryA7 acr-11 strB2 (respectively, deficiency for purine, and resistance to tetracycline, erythromycin, acriflavine, and streptomycin). Excluding the genes for acriflavine resistance, acr-2 and acr-11, resistance loci in N. erythropolis were not allelic to and showed lateral displacement from genes controlling phenotypically similar resistance in N. canicruria. Evidence for some lack of homology between N. erythropolis and N. canicruria genomes was found. Recombination phenomena between the nocardial species was postulated to occur as a result of formation of a heterogenomic zygote in which new combinations were produced. Production of selectable, haploid recombinants was ascribed to subsequent haploidization of the zygote.     

A Linkage Map of Endogenous Murine Leukemia Proviruses

Thirty endogenous proviruses belonging to the modified polytropic (Mpmv) class of murine leukemia virus (MLV) were identified by proviral-cellular DNA junction fragment segregation in several sets of recombinant inbred mice. Twenty-six Mpmv loci were mapped to chromosomal regions by matching proviral strain distribution patterns to those of previously assigned genes. Like other endogenous nonecotropic MLVs, Mpmv loci were present on several chromosomes in all strains examined. We pooled recombinant inbred strain linkage data from 110 MLV loci and selected marker genes in order to construct a chromosomal linkage map. Every mouse chromosome was found to harbor at least one proviral insertion, and several regions contained multiple integrations. However, the overall distribution of the 110 mapped proviruses did not deviate significantly from a random distribution. Because of their polymorphism in inbred strains of mice, and the ability to score as many as 57 proviruses per strain using only three hybridization probes, the nonecotropic MLVs mapped in common strains of mice offer a significant advantage over older methods (e.g., biochemical or individual restriction fragment polymorphisms) as genetic markers. These endogenous insertion elements should also be useful for assessing strain purity, and for studying the relatedness of common and not-so-common inbred strains.     

Electrophoretic Karyotype and Linkage Groups of the Amoeboflagellate Naegleria gruberi

ABSTRACT. We have constructed a molecular karyotype for two strains of Naegleria gruberi using pulsed field gel electrophoresis. Each strain has about 23 chromosomes, considerably more than any previous estimate. These chromosomes range in size from 400 kilobasepairs to over 2,000 kilobasepairs. In Naegleria , construction of the DNA karyotype depends on assessment of the anomalous electrophoretic mobility of the circular ribosomal RNA genes. We have determined the chromosomal locations of an identified unique gene (flagellar calmodulin) and four identified multigene families (α- and β-tubulin, actin, ubiquitin), as well as three differentially expressed genes of unknown functions. The ca. 12 actin genes are dispersed over at least seven chromosomes, whereas the majority of the more than eight α-tubulin genes are confined to a single chromosome. The ubiquitin genes are found on five chromosomes in one strain and seven in the other and the β-tubulin genes are on three or four. Our observations provide a foundation for molecular genetic studies in this organism.     

家族性不宁腿综合征候选基因的连锁分析

不宁腿综合征（restless legs syndrome,RLS)是以下肢部出现蚁行样及酸、麻、胀等不适感而使肢体不得休息为特征的一组病症。由于症状常在晚间发作并导致运动不安,患者长期入睡困难,经受严重的继发性失眠。作为一种常见的神经系统疾病,RLS发病率高达5％,其中原发性RLS多呈阳性家族史,表现为单基因决定的常染色体显性遗传。现在,人们普遍认为RLS的发生很可能与神经系统内多巴胺能功能异常和脑内铁缺乏有关,并初步建立了脑铁－多巴胺能系统的致病模型。为了探求脑铁－多巴胺能系统在RLS中的作用,选择了与脑铁－多巴胺能系统相关的16个疾病侯选基因,在每个候选基因附近染色体区域内选取若干个微卫星多态标记,应用微卫星引物荧光标记－基因扫描技术,对一个汉族家族性不宁腿综合征家系进行了基因分型和常染色体显性遗传模式下的连锁分析,试图从分子遗传学层面上确认或排除一些可能与RLS相关的重要侯选基因。结果显示,当重组系数θ=0.00时,LOD值均小于－2.00,所选位点与家族性不宁腿综合征不连锁。由此得出结论,在本家系中,所有候选基因均与家族性不宁腿综合征的发病无关,家族性不宁腿综合征可能是由其他多巴胺传导和脑铁代谢相关基因所致,或是存在全新的致病机制参与RLS的发生。     

Linkage groups inAscobolus immersus

Thirty-two genes (31 mutants and themt gene) have been mapped in 9 linkage groups. There are at least 28 loci distributed as follows: two loci each in groups I, IV, V, VII, VIII and IX; 3 in group VI; 8 or more loci in group II; and 5 loci in group III.Supported by Grant GB-3325 from the National Science Foundation.     

Linkage mapping of gene-associated SNPs to pig chromosome 11

Single nucleotide polymorphisms (SNPs) were discovered in porcine expressed sequence tags (ESTs) orthologous to genes from human chromosome 13 (HSA13) and predicted to be located on pig chromosome 11 (SSC11). The SNPs were identified as sequence variants in clusters of EST sequences from pig cDNA libraries constructed in the Sino-Danish pig genome project. In total, 312 human gene sequences from HSA13 were used for similarity searches in our pig EST database. Pig ESTs showing significant similarity with HSA13 genes were clustered and candidate SNPs were identified. Allele frequencies for 26 SNPs were estimated in a group of 80 unrelated pigs from Danish commercial pig breeds: Duroc, Hampshire, Landrace and Large White. Eighteen of the 26 SNPs genotyped in the PiGMaP Reference Families were mapped by linkage analysis to SSC11. The EST-based SNPs published here are new genetic markers useful for linkage and association studies in commercial and experimental pig populations. This study represents the first gene-associated SNP linkage map of pig chromosome 11 and adds new comparative mapping information between SSC11 and HSA13. Furthermore, our data facilitate future studies aimed at the identification of interesting regions on pig chromosome 11, positional cloning and fine mapping of quantitative trait loci in pig.     

Linkage and Association Studies of Prostate Cancer Susceptibility: Evidence for Linkage at 8p22-23

Multiple lines of evidence have implicated the short arm of chromosome 8 as harboring genes important in prostate carcinogenesis. Although most of this evidence comes from the identification of frequent somatic alterations of 8p loci in prostate cancer cells (e.g., loss of heterozygosity), studies have also suggested a role for 8p genes in mediation of inherited susceptibility to prostate cancer. To further examine this latter possibility, we performed linkage analyses, in 159 pedigrees affected by hereditary prostate cancer (HPC), using 24 markers on the short arm of chromosome 8. In the complete set of families, evidence for prostate cancer linkage was found at 8p22-23, with a peak HLOD of 1.84 (P=.004), and an estimate of the proportion of families linked (alpha) of 0.14, at D8S1130. In the 79 families with average age at diagnosis >65 years, an allele-sharing LOD score of 2.64 (P=.0005) was observed, and six markers spanning a distance of 10 cM had LOD scores >2.0. Interestingly, the small number of Ashkenazi Jewish pedigrees (n=11) analyzed in this study contributed disproportionately to this linkage. Mutation screening in HPC probands and association analyses in case subjects (a group that includes HPC probands and unrelated case subjects) and unaffected control subjects were carried out for the putative prostate cancer-susceptibility gene, PG1, previously localized to the 8p22-23 region. No statistical differences in the allele, genotype, or haplotype frequencies of the SNPs or other sequence variants in the PG1 gene were observed between case and control subjects. However, case subjects demonstrated a trend toward higher homozygous rates of less-frequent alleles in all three PG1 SNPs, and overtransmission of a PG1 variant to case subjects was observed. In summary, these results provide evidence for the existence of a prostate cancer-susceptibility gene at 8p22-23. Evaluation of the PG1 gene and other candidate genes in this area appears warranted.