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1.
Shi XW Fitzsimmons CJ Genêt C Prather R Whitworth K Green JA Tuggle CK 《Animal genetics》2001,32(4):205-209
A comparative study of human chromosome 17 (HSA17) and pig chromosome 12 (SSC12) was conducted using both somatic cell hybrid panel (SCHP) and radiation hybrid (RH) panel analysis. Sequences from an expressed sequence tag (EST) project in pig reproduction were examined and six genes and ESTs originally believed to map to HSA17 were selected for this study. The genes/ESTs were TATA box binding protein-associated factor (TAF2N/RBP56), alpha-2-plasmin inhibitor (SERPINF2/PLI), H3 histone family 3B (H3F3B), aminopeptidase puromycin sensitive (NPEPPS), an expressed sequence tag (ESTMI015) and P311 protein (P311). The SCHP analysis mapped five genes/ESTs (TAF2N, H3F3B, SERPINF2, NPEPPS and ESTMI015) to SSC12q11-q15 and SSC12p11-p15 with 100% concordance, and assigned P311 to SSC2 (1/2q24)-q29 with 100% concordance. Radiation hybrid analysis of all six genes confirmed the SCHP mapping results, with average retention frequency of 25%. Recent human sequence data demonstrated that P311 is actually located on HSA5q. As HSA5q and SSC2q show conserved syntenic regions predicted from bi-directional painting, our P311 mapping data is consistent with these results. An expanded comparative SSC12 RH map integrating the five new type I markers and 23 previously mapped loci was established using a LOD score threshold of 4.8. The gene order of the five genes/ESTs on the SSC12 framework RH map (H3F3B-ESTMI015-NPEPPS-TAF2N-SERPINF2) is identical to the HSA17 GB4 map but with inversion of the map as conventionally drawn. 相似文献
2.
A high-resolution radiation hybrid map of porcine chromosome 6 总被引:2,自引:0,他引:2
Cao H Robinson JA Jiang Z Melville JS Golovan SP Jones MW Verrinder Gibbins AM 《Animal genetics》2004,35(5):367-378
A high-resolution comprehensive map was constructed for porcine chromosome (SSC) 6, where quantitative trait loci (QTL) for reproduction and meat quality traits have been reported to exist. A radiation hybrid (RH) map containing 105 gene-based markers and 15 microsatellite markers was constructed for this chromosome using a 3000-rad porcine/hamster RH panel. In total, 40 genes from human chromosome (HSA) 1p36.3-p22, 29 from HSA16q12-q24, 17 from HSA18p11.3-q12 and 19 from HSA19q13.1-q13.4 were assigned to SSC6. All primers for these gene markers were designed based on porcine gene or EST sequences, and the orthologous status of the gene markers was confirmed by direct sequencing of PCR products amplified from separate Meishan and Large White genomic DNA pools. The RH map spans SSC6 and consists of six linkage groups created by using a LOD score threshold of 4. The boundaries of the conserved segments between SSC6 and HSA1, 16, 18 and 19 were defined more precisely than previously reported. This represents the most comprehensive RH map of SSC6 reported to date. Polymorphisms were detected for 38 of 105 gene-based markers placed on the RH map and these are being exploited in ongoing chromosome wide scans for QTL and eventual fine mapping of genes associated with prolificacy in a Meishan x Large White multigenerational commercial population. 相似文献
3.
Annemieke P. Rattink Marilyne Faivre Bart J. Jungerius Martien A.M. Groenen Barbara Harlizius 《Mammalian genome》2001,12(5):366-370
A high-resolution comparative map was constructed for porcine Chromosome (SSC) 2, where a QTL for back fat thickness (BFT)
is located. A radiation hybrid (RH) map containing 33 genes and 25 microsatellite markers was constructed for this chromosome
with a 3000-rad porcine RH panel. In total, 16 genes from human Chromosome (HSA) 11p, HSA19p, and HSA5q were newly assigned
to SSC2. One linkage group was observed at LOD 3.0, and five linkage groups at LOD 4.0. Comparison of the porcine RH map with
homologous human gene orders identified four conserved segments between SSC2 and HSA11, HSA19, and HSA5. Concerning HSA11,
a rearrangement of gene order is observed. The segment HSA11p15.4-q13 is inverted on SSC2 when compared with the distal tip
of SSC2p, which is homologous to HSA11p15.5. The boundaries of the conserved segments between human and pig were defined more
precisely. This high-resolution comparative map will be a valuable tool for further fine mapping of the QTL area.
Received: 10 November 2000 / Accepted: 23 January 2001 相似文献
4.
Bosak N Yamomoto R Fujisaki S Faraut T Kiuchi S Hiraiwa H Hayashi T Yasue H 《Cytogenetic and genome research》2005,108(4):317-321
The human chromosome (HSA)19q region has been shown to correspond to swine chromosome (SSC) 6q11-->q21 by bi-directional chromosomal painting and gene mapping. However, since the precise correspondence has not been determined, 26 genes localized in HSA19q13.3-->q13.4 were assigned to the SSC6 region mainly by radiation hybrid (RH) mapping, and additionally, by somatic cell hybrid panel (SCHP) mapping, and fluorescent in situ hybridization (FISH). Out of the 26 genes, 24 were assigned to a swine RH map with LOD scores greater than 6 (threshold of significance). The most likely order of the 24 genes along SSC6 was calculated by CarthaGene, revealing that the order is essentially the same as that in HSA19q13.3-->q13.4. For AURKC and RPS5 giving LOD scores not greater than 6, SCHP mapping and FISH were additionally performed; SCHP mapping assigned AURKC and RPS5 to SSC6q22-->q23 and SSC6q21, respectively, which is consistent with the observation of FISH. Consequently, all the genes (26 genes) examined in the present study were shown to localize in SSC6q12-->q23, and the order of the genes along the chromosomes was shown to be essentially the same in swine and human, though several intrachromosomal rearrangements were observed between the species. 相似文献
5.
Noriyuki Hamasima Ayumi Mikawa Hideaki Suzuki Kohei Suzuki Hirohide Uenishi Takashi Awata 《Mammalian genome》2008,19(1):51-60
We constructed a 5000-rad comprehensive radiation hybrid (RH) map of the porcine (Sus scrofa) genome and compared the results with the human genome. Of 4475 typed markers, 4016 (89.7%) had LOD >5 compared with the
markers used in our previous RH map by means of two-point analysis and were grouped onto the 19 porcine chromosomes (SSCs).
All mapped markers had LOD >3 as determined by RHMAPPER analysis. The current map comprised 430 microsatellite (MS) framework
markers, 914 other MS markers, and 2672 expressed sequence tags (ESTs). The whole-genome map was 8822.1 cR in length, giving
an average marker density of 0.342 Mb/cR. The average retention frequency was 35.8%. Using BLAST searches of porcine ESTs
against the RefSeq human nucleotide and amino acid sequences (release 22), we constructed high-resolution comparative maps
of each SSC and each human chromosome (HSA). The average distance between ESTs in the human genome was 1.38 Mb. SSC contained
50 human chromosomal syntenic groups, and SSC11, SSC12, and SSC16 were only derived from the HSA13q, HSA17, and HSA5 regions,
respectively. Among 38 porcine terminal regions, we found that at least 20 regions have been conserved between the porcine
and human genomes; we also found four paralogous regions for the major histocompatibility complex (MHC) on SSC7, SSC2, SSC4,
and SSC1.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
6.
RPLP0基因编码酸性核糖体磷蛋白大亚基P0, 是核糖体60S亚基的组成成分之一。从本室构建的猪胚胎骨骼肌cDNA文库中分离得到猪RPLP0基因的全长cDNA,并提交 GenBank 数据库。比较猪 RPLP0 基因和人及小鼠同源基因的cDNA序列和蛋白质序列,结果表明该基因在 3 个物种中具有高的相似性。用 PCR-RFLP 方法在猪 RPLP0基因cDNA 545处检测到 C→A 的单碱基突变,为 Csp6Ⅰ的酶切位点。统计分析结果表明 3 种基因型 (AA,AC,CC)在外来品种杜洛克,大约克, 长白和中国地方品种通城猪,小梅山,玉山猪中的分布各不相同。同时使用体细胞杂种板(SCHP)和辐射杂种板(IMpRH) 对 RPLP0 基因进行染色体定位,该基因被定位于 SSC 14q22-q24 并且和SW1321微卫星标志紧密连锁 (25cR, LOD = 14.54)。 相似文献
7.
To provide a gene-based comparative map and to examine a porcine genome assembly using bacterial artificial chromosome-based sequence, we have attempted to assign 128 genes localized on human chromosome 14q (HSA14q) to a porcine 7000-rad radiation hybrid (IMpRH) map. This study, together with earlier studies, has demonstrated the following. (i) 126 genes were incorporated into two SSC7 RH linkage groups by C artha G ene analysis. (ii) In the remaining two genes, TOX4 linked to TCRA located in SSC7 by two-point analysis, whereas SIP1 showed no significant linkage with any gene/marker registered in the IMpRH Web Server. (iii) In the two groups, the gene clusters located from 19.9 to 36.5 Mb on HSA14q11.2-q13.3 and from 64.0 to 104.3 Mb on HSA14q23-q32.33 respectively were assigned to SSC7q21-q26. (iv) Comparison of the gene order between the present RH map and the latest porcine sequence assembly revealed some inconsistencies, and a redundant arrangement of 16 genes in the sequence assembly. 相似文献
8.
Fakiola M Mishra A Rai M Singh SP O'Leary RA Ball S Francis RW Firth MJ Radford BT Miller EN Sundar S Blackwell JM 《PloS one》2010,5(12):e15807
Background
Genome wide linkage studies (GWLS) have provided evidence for loci controlling visceral leishmaniasis on Chromosomes 1p22, 6q27, 22q12 in Sudan and 6q27, 9p21, 17q11-q21 in Brazil. Genome wide studies from the major focus of disease in India have not previously been reported.Methods and Findings
We undertook a GWLS in India in which a primary ∼10 cM (515 microsatellites) scan was carried out in 58 multicase pedigrees (74 nuclear families; 176 affected, 353 total individuals) and replication sought in 79 pedigrees (102 nuclear families; 218 affected, 473 total individuals). The primary scan provided evidence (≥2 adjacent markers allele-sharing LOD≥0.59; nominal P≤0.05) for linkage on Chromosomes 2, 5, 6, 7, 8, 10, 11, 20 and X, with peaks at 6p25.3-p24.3 and 8p23.1-p21.3 contributed to largely by 31 Hindu families and at Xq21.1-q26.1 by 27 Muslim families. Refined mapping confirmed linkage across all primary scan families at 2q12.2-q14.1 and 11q13.2-q23.3, but only 11q13.2-q23.3 replicated (combined LOD = 1.59; P = 0.0034). Linkage at 6p25.3-p24.3 and 8p23.1-p21.3, and at Xq21.1-q26.1, was confirmed by refined mapping for primary Hindu and Muslim families, respectively, but only Xq21.1-q26.1 replicated across all Muslim families (combined LOD 1.49; P = 0.0045). STRUCTURE and SMARTPCA did not identify population genetic substructure related to religious group. Classification and regression tree, and spatial interpolation, analyses confirm geographical heterogeneity for linkages at 6p25.3-p24.3, 8p23.1-p21.3 and Xq21.1-q26.1, with specific clusters of families contributing LOD scores of 2.13 (P = 0.0009), 1.75 (P = 0.002) and 1.84 (P = 0.001), respectively.Conclusions
GWLS has identified novel loci that show geographical heterogeneity in their influence on susceptibility to VL in India. 相似文献9.
Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians. 总被引:12,自引:6,他引:6 下载免费PDF全文
R A Norman P A Tataranni R Pratley D B Thompson R L Hanson M Prochazka L Baier M G Ehm H Sakul T Foroud W T Garvey D Burns W C Knowler P H Bennett C Bogardus E Ravussin 《American journal of human genetics》1998,62(3):659-668
An autosomal genomic scan to search for linkage to obesity and energy metabolism was completed in Pima Indians, a population prone to obesity. Obesity was assessed by percent body fat (by hydrodensitometry) and fat distribution (the ratio of waist circumference to thigh circumference). Energy metabolism was measured in a respiratory chamber as 24-h metabolic rate, sleeping metabolic rate, and 24-h respiratory quotient (24RQ), an indicator of the ratio of carbohydrate oxidation to fat oxidation. Five hundred sixteen microsatellite markers with a median spacing of 6.4 cM were analyzed, in 362 siblings who had measurements of body composition and in 220 siblings who had measurements of energy metabolism. These comprised 451 sib pairs in 127 nuclear families, for linkage analysis to obesity, and 236 sib pairs in 82 nuclear families, for linkage analysis to energy metabolism. Pointwise and multipoint methods for regression of sib-pair differences in identity by descent, as well as a sibling-based variance-components method, were used to detect linkage. LOD scores >=2 were found at 11q21-q22, for percent body fat (LOD=2.1; P=.001), at 11q23-q24, for 24-h energy expenditure (LOD=2.0; P=.001), and at 1p31-p21 (LOD=2.0) and 20q11.2 (LOD=3.0; P=.0001), for 24RQ, by pointwise and multipoint analyses. With the variance-components method, the highest LOD score (LOD=2.3 P=.0006) was found at 18q21, for percent body fat, and at 1p31-p21 (LOD=2.8; P=.0003), for 24RQ. Possible candidate genes include LEPR (leptin receptor), at 1p31, and ASIP (agouti-signaling protein), at 20q11.2. 相似文献
10.
Marie-Françoise Rousseau-Merck Ahmed Zahraoui Nicolas Touchot Armand Tavitian Roland Berger 《Human genetics》1991,86(4):350-354
Summary The human RAB genes share structural and biochemical properties with the RAS gene superfamily. The encoded RAB proteins show 38 to 75% amino acid identity with the yeast YPT1 and SEC4 gene products. We used four human RAB-cDNAs, RAB3B, RAB4, RAB5 and RAB6, to map the corresponding genes on human chromosomes. These genes were assigned to 1p32-p31, 1q42-q43, 3p24-p22 and 2q14-q21, respectively, by in situ hybridization. 相似文献
11.
Marie-Françoise Rousseau-Merck Josette Hillion Philippe Jonveaux Philippe Couillin Paule Seité Hans-Jürgen Thiesen Roland Berger 《Human genetics》1993,92(6):583-587
Nine KOX zinc finger genes were localized on four human chromosomes by in situ hybridization of cDNA probes to metaphase chromosomes. KOX1 (ZNF10), KOX11 (ZNF18), and KOX12 (ZNF19) were mapped to chromosome bands 12q24.33, 17p13-p12, and 16q22-q23, respectively. Six other KOX genes were localized on chromosome 19: KOX6 (ZNF14) and KOX13 (ZNF20) to 19p13.3-p13.2, KOX5 (ZNF13) and KOX22 (ZNF27) to 19q13.2-qter, and KOX24 (ZNF28) and KOX28 (ZNF30) to 19q13.4. Pulsed field gel electrophoresis experiments showed that the pairs of KOX genes found on the chromosome bands 12q24.33, 16q22-q23, 19p13.3-p13.2, or 19q13.3-qter lie within 200–300 kb DNA fragments. This suggests the existence of KOX gene clusters on these chromosomal bands. 相似文献
12.
运用比较基因组学的方法,根据人的CDC16基因序列设计引物,从大围子猪和宁乡猪基因组DNA分离了CDC16基因内含子4和内含子8(GenBank收录号为AY880670和DQ206823),通过扩增体细胞杂种克隆板上27个样品和辐射杂种克隆板上118个样品,确定了CDC16基因在猪染色体上的物理位置,首次将CDC16基因物理定位于猪SSC11 q11-17.该基因与微卫星SW1452标记紧密连锁,LOD值为16.08,存留率为22%,在放射杂交图谱上的图距为62 cR.CDC16基因区间定位结果与精细定位结果相一致,也与比较定位结果相一致,进一步验证了猪11号染色体和人13号染色体大部分片段存在同源性,这为该基因的克隆及和功能研究打下坚实基础. 相似文献
13.
CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder 总被引:7,自引:0,他引:7
Verkerk AJ Mathews CA Joosse M Eussen BH Heutink P Oostra BA;Tourette Syndrome Association International Consortium for Genetics 《Genomics》2003,82(1):1-9
Gilles de la Tourette syndrome (GTS) is a sporadic or inherited complex neuropsychiatric disorder characterized by involuntary motor and vocal tics. There is comorbidity with disorders like obsessive compulsive disorder and attention deficit hyperactivity disorder. Until now linkage analysis has pointed to a number of chromosomal locations, but has failed to identify a clear candidate gene(s). We have investigated a GTS family with a complex chromosomal insertion/translocation involving chromosomes 2 and 7. The affected father [46,XY,inv(2) (p23q22),ins(7;2) (q35-q36;p21p23)] and two affected children [46,XX,der(7)ins(7;2)(q35-q36;p21p23) and 46,XY,der(7)ins(7;2)(q35-q36;p213p23)] share a chromosome 2p21-p23 insertion on chromosome 7q35-q36, thereby interrupting the contactin-associated protein 2 gene (CNTNAP2). This gene encodes a membrane protein located in a specific compartment at the nodes of Ranvier of axons. We hypothesize that disruption or decreased expression of CNTNAP2 could lead to a disturbed distribution of the K(+) channels in the nervous system, thereby influencing conduction and/or repolarization of action potentials, causing unwanted actions or movements in GTS. 相似文献
14.
A novel linkage to generalized vitiligo on 4q13-q21 identified in a genomewide linkage analysis of Chinese families 总被引:5,自引:0,他引:5 下载免费PDF全文
Chen JJ Huang W Gui JP Yang S Zhou FS Xiong QG Wu HB Cui Y Gao M Li W Li JX Yan KL Yuan WT Xu SJ Liu JJ Zhang XJ 《American journal of human genetics》2005,76(6):1057-1065
Generalized vitiligo is a common, autoimmune, familial-clustering depigmentary disorder of the skin and hair that results from selective destruction of melanocytes. Generalized vitiligo is likely a heterogeneous disease, with five susceptibility loci reported so far--on chromosomes 1p31, 6p21, 7q, 8p, and 17p13--in white populations. To investigate vitiligo susceptibility loci in the Chinese population, we performed a genomewide linkage analysis in 57 multiplex Chinese families, each with at least two affected siblings, and we identified interesting linkage evidence on 1p36, 4q13-q21, 6p21-p22, 6q24-q25, 14q12-q13, and 22q12. Subsequently, to extract more linkage information, we investigated our initial genomewide linkage findings in a follow-up analysis of 49 new families and additional markers. Our initial genomewide linkage analysis and our subsequent follow-up analysis have identified a novel linkage to vitiligo on 4q13-q21, with highly significant linkage evidence (a nonparametic LOD score of 4.62 [P=.000003] and a heterogeneity LOD score of 4.01, under a recessive inheritance model), suggesting that 4q13-q21 likely harbors a major susceptibility locus for vitiligo in the Chinese population. We observed a minimal overlap between the linkage results of our current genomewide analysis in the Chinese population and the results of previous analyses in white populations, and we thus hypothesize that, as a polygenic disorder, vitiligo may be associated with great genetic heterogeneity and a substantial difference in its genetic basis between ethnic populations. 相似文献
15.
Nanjangud G Rao PH Teruya-Feldstein J Donnelly G Qin J Mehra S Jhanwar SC Zelenetz AD Chaganti RS 《Cytogenetic and genome research》2007,118(2-4):337-344
We analyzed a cohort of 61 follicular lymphomas (FL) with an abnormal G-banded karyotype by spectral karyotyping (SKY) to better define the chromosome instability associated with the t(14;18)(q32;q21) positive and negative subsets of FL and histologic grade. In more than 70% of the patients, SKY provided additional cytogenetic information and up to 40% of the structural abnormalities were revised. The six most frequent breakpoints in both SKY and G-banding analyses were 14q32, 18q21, 3q27, 1q11-q21, 6q11-q15 and 1p36 (15-77%). SKY detected nine additional sites (1p11-p13, 2p11-p13, 6q21, 8q24, 6q21, 9p13, 10q22-q24, 12q11-q13 and 17q11-q21) at an incidence of >10%. In addition to the known recurring translocations, t(14;18)(q32;q21) [70%], t(3;14)(q27;q32) [10%], t(1;14)(q21;q32) [5%] and t(8;14)(q24;q32) [2%] and their variants, 125 non-IG gene translocations were identified of which four were recurrent within this series. In contrast to G-banding analysis, SKY revealed a greater degree of karyotypic instability in the t(14;18) (q32;q21) negative subset compared to the t(14;18)(q32;q21) positive subset. Translocations of 3q27 and gains of chromosome 1 were significantly more frequent in the former subset. SKY also allowed a better definition of chromosomal imbalances, thus 37% of the deletions detected by G-banding were shown to be unbalanced translocations leading to gain of genetic material. The majority of recurring (>10%) imbalances were detected at a greater (2-3 fold) incidence by SKY and several regions were narrowed down, notably at gain 2p13-p21, 2q11-q21, 2q31-q37, 12q12-q15, 17q21-q25 and 18q21. Chromosomal abnormalities among the different histologic grades were consistent with an evolution from low to high grade disease and breaks at 6q11-q15 and 8q24 and gain of 7/7q and 8/8q associated significantly with histologic progression. This study also indicates that in addition to gains and losses, non-IG gene translocations involving 1p11-p13, 1p36, 1q11-q21, 8q24, 9p13, and 17q11-q21 play an important role in the histologic progression of FL with t(14;18)(q32;q21) and t(3q27). 相似文献
16.
Nitish Sarker Rachel J. Hawken Seiya Takahashi Leeson J. Alexander Takashi Awata Lawrence B. Schook Hiroshi Yasue 《Mammalian genome》2001,12(7):524-527
Several quantitative trait loci (QTLs) (vertebrate number, birth weight, age at puberty, growth rate, gestation length, and
backfat depth) have been independently mapped to the distal region of swine Chromosome (SSC) 1q in several resource populations.
In order to improve the map resolution and refine these QTLs more precisely on SSC1q, we have isolated and mapped additional
microsatellites (ms), using chromosome microdissection and radiation hybrid (RH) mapping. Five copies of the telomeric region
of SSC1q were microdissected from metaphase spreads and pooled. The chromosomal fragment DNA was randomly amplified by using
degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR), enriched for ms, and subcloned into a PCR vector. Screening
of subsequent clones with ms probes identified 23 unique ms sequences. Fifteen of these (65%) were subjected to radiation
hybrid (RH) mapping by using the INRA-University of Minnesota porcine RH panel (IMpRH); and the remaining eight were not suited
for the RH mapping. Twelve microsatellites were assigned to SSC1q telomeric region of IMpRH map (LOD >6), and three remain
unlinked (LOD <6). Out of the 15 microsatellite markers, 9 were polymorphic in NIAI reference population based on the Meishan
and G?ttingen miniature pig. In summary, we have used microdissection and radiation hybrid mapping to clone and map 12 new
microsatellites to the swine gene map to increase the resolution of SSC1q in the region of known QTLs.
Received: 19 December 2000 / Accepted: 28 February 2001 相似文献
17.
Genomewide search for genes influencing percent body fat in Pima Indians: suggestive linkage at chromosome 11q21-q22. Pima Diabetes Gene Group. 总被引:1,自引:0,他引:1 下载免费PDF全文
R A Norman D B Thompson T Foroud W T Garvey P H Bennett C Bogardus E Ravussin 《American journal of human genetics》1997,60(1):166-173
On the basis of accumulating evidence that obesity has a substantial genetic component, a genomewide search for linkages of DNA markers to percent body fat is ongoing in Pima Indians, a population with a very high prevalence of obesity. An initial screen of the genome (>600 markers in 874 individuals) has been completed using highly polymorphic markers (mean heterozygosity = .67). Reported here are the sib-pair linkage results for percent body fat (277 siblings), the best available indicator of overall obesity. Single-marker linkages to percent body fat were evaluated by sib-pair analysis for quantitative traits. From these analyses, the best evidence of genes influencing body fat came from markers at chromosome 11q21-q22 and 3p24.2-p22 (P = .001; LOD = 2.0). Regions flanking these markers were further investigated by multipoint linkage. The evidence for linkage at 11q21-q22 increased to P = .0002 (LOD = 2.8), peaking between markers D11S2000 and D11S2366. Evidence for linkage at 3p24.2-p22 did not change. No association was detected for any marker in the region. Although several genes are known in the 11q21-q22 region, none have been implicated as candidate genes for obesity. 相似文献
18.
Genomewide linkage scan of 409 European-ancestry and African American families with schizophrenia: suggestive evidence of linkage at 8p23.3-p21.2 and 11p13.1-q14.1 in the combined sample 下载免费PDF全文
Suarez BK Duan J Sanders AR Hinrichs AL Jin CH Hou C Buccola NG Hale N Weilbaecher AN Nertney DA Olincy A Green S Schaffer AW Smith CJ Hannah DE Rice JP Cox NJ Martinez M Mowry BJ Amin F Silverman JM Black DW Byerley WF Crowe RR Freedman R Cloninger CR Levinson DF Gejman PV 《American journal of human genetics》2006,78(2):315-333
We report the clinical characteristics of a schizophrenia sample of 409 pedigrees--263 of European ancestry (EA) and 146 of African American ancestry (AA)--together with the results of a genome scan (with a simple tandem repeat polymorphism interval of 9 cM) and follow-up fine mapping. A family was required to have a proband with schizophrenia (SZ) and one or more siblings of the proband with SZ or schizoaffective disorder. Linkage analyses included 403 independent full-sibling affected sibling pairs (ASPs) (279 EA and 124 AA) and 100 all-possible half-sibling ASPs (15 EA and 85 AA). Nonparametric multipoint linkage analysis of all families detected two regions with suggestive evidence of linkage at 8p23.3-q12 and 11p11.2-q22.3 (empirical Z likelihood-ratio score [Z(lr)] threshold >/=2.65) and, in exploratory analyses, two other regions at 4p16.1-p15.32 in AA families and at 5p14.3-q11.2 in EA families. The most significant linkage peak was in chromosome 8p; its signal was mainly driven by the EA families. Z(lr) scores >2.0 in 8p were observed from 30.7 cM to 61.7 cM (Center for Inherited Disease Research map locations). The maximum evidence in the full sample was a multipoint Z(lr) of 3.25 (equivalent Kong-Cox LOD of 2.30) near D8S1771 (at 52 cM); there appeared to be two peaks, both telomeric to neuregulin 1 (NRG1). There is a paracentric inversion common in EA individuals within this region, the effect of which on the linkage evidence remains unknown in this and in other previously analyzed samples. Fine mapping of 8p did not significantly alter the significance or length of the peak. We also performed fine mapping of 4p16.3-p15.2, 5p15.2-q13.3, 10p15.3-p14, 10q25.3-q26.3, and 11p13-q23.3. The highest increase in Z(lr) scores was observed for 5p14.1-q12.1, where the maximum Z(lr) increased from 2.77 initially to 3.80 after fine mapping in the EA families. 相似文献
19.
Satu Kuokkanen Michele Gschwend John D. Rioux Mark J. Daly Joseph D. Terwilliger Pentti J. Tienari Juhani Wikström Jorma Palo Lincoln D. Stein Thomas J. Hudson Eric S. Lander Leena Peltonen 《American journal of human genetics》1997,61(6):1379-1387
Multiple sclerosis (MS) is a neurological, demyelinating disorder with a putative autoimmune etiology. It is thought to be a multifactorial disease with a complex mode of inheritance. Here we report the results of a two-stage genomewide scan for loci predisposing to MS. The first stage of the screen, with a low-resolution map, was performed in a selection of 16 pedigrees collected from an isolated Finnish population. Multipoint, non-parametric linkage analysis of the 328 markers did not reveal statistically significant results. However, 10 slightly interesting regions (P = .1-.15) emerged, including our previous findings of the HLA complex on 6p21 and a putative locus on 5p14-p12. Eight of these novel regions were further analyzed by use of denser marker maps, in the second stage of the scan. For the chromosomal regions 4cen, 11tel, and 17q, the statistical significance increased, but not conclusively; for 2q32 and 10q21, the statistical significance did not change. Accordingly, genotyping of the high-density markers in these regions was performed, and the data were analyzed by use of two-point, parametric linkage analysis using the complete pedigree information of the 21 Finnish multiplex families. We detected suggestive evidence for a predisposing locus on chromosomal region 17q22-q24. Several markers on 17q22-q24 yielded positive LOD scores, with the maximum LOD score (Zmax) occurring with D17S807 (Zmax = 2.8, theta = .04; dominant model). Interestingly, a suggestive linkage between MS and the markers on 17q22-q24 was also revealed by a recent genomewide scan in MS families from the United Kingdom. 相似文献