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Identification of a hypervariable microsatellite polymorphism within D9S15 tightly linked to Friedrich's ataxia.

We have identified a hypervariable microsatellite sequence within the chromosome 9 marker MCT112 (D9S15), which we have previously shown to be tightly linked to Friedreich's ataxia (FRDA). The system detects 7 alleles ranging in size from 195 to 209 base pairs, and substantially increases informativity at the MCT112 locus. This enhances its use for genetic counselling in affected families. Recalculated combined linkage data between the FRDA locus and MCT112 gives a maximal lod score of 66.91 at a recombination fraction of theta = 0). There is no evidence of linkage disequilibrium.

Linkage of epidermolysis bullosa simplex to keratin gene loci.

Epidermolysis bullosa simplex (EBS) is an autosomal dominant disorder characterised by intraepidermal blistering of the skin. Two families with Weber-Cockayne EBS have been analysed for linkage to keratin gene loci. In the first family, linkage was found to chromosome 17 markers flanking the keratin 14 gene (D17S74: Zmax = +2.45, theta = 0.10; COL1A1: Zmax = +0.97, theta = 0.00) and markers near the keratin 5 gene on chromosome 12 were excluded (D12S17: Z less than -2.0, theta = 0.08; COL2A1: Z less than -2.0, theta = 0.13). In contrast, the second family showed linkage to the region containin

Heterozygous Seryl-tRNA Synthetase 1 Variants Cause Charcot-Marie-Tooth Disease.

OBJECTIVE: Despite the increasing number of genes associated with Charcot-Marie-Tooth (CMT) disease, many patients currently still lack appropriate genetic diagnosis for this disease. Autosomal dominant mutations in aminoacyl-tRNA synthetases (ARSs) have been implicated in CMT. Here, we describe causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) for 3 families affected with CMT. METHODS: Whole-exome sequencing was performed in 16 patients and 14 unaffected members of 3 unrelated families. The functional impact of the genetic variants identified was investigated usi

A haplotypic variant at the IRGM locus and rs11747270 are related to the susceptibility for chronic periodontitis.

OBJECTIVE AND DESIGN: Immunity-regulated GTPase M (IRGM) plays a critical role in the defense against intracellular bacteria by regulating autophagy formation. This direct genetic association study aimed to determine whether variants at the IRGM genetic locus are associated with chronic periodontitis. MATERIALS AND SUBJECTS: Using PCR and melting curve analysis 390 periodontitis patients and 770 healthy controls have been genotyped regarding six polymorphisms in the IRGM gene (rs13361189, rs10065172, rs4958847, rs1000113, rs11747270, rs931058). RESULTS: Frequency distribution of alleles and

Autosomal dominant Parkinson's disease in a large German pedigree.

OBJECTIVE: While several genes have been identified to cause Parkinson's disease (PD), monogenic forms explain only a small proportion of cases. We report clinical and genetic results in a large family with late-onset autosomal dominant PD. METHODS: Thirty-eight family members of a five-generation Northern German PD family underwent a detailed neurologic examination, and transcranial sonography was performed in fifteen of them. Comprehensive mutation analysis of known PD-causing genes and a genome-wide linkage analysis were performed. RESULTS: Late-onset definite PD was found in five subject

Linkage analysis and a novel COL4A5 mutation in a large Turkish family with Alport syndrome.

BACKGROUND: Alport syndrome (AS) is a renal disease that is characterized by proteinuria and progressive renal failure, and often accompanie … COL4A5 markers. In addition, COL4A5 gene sequence analysis was performed in the proband. RESULTS: Genetic linkage analysis demonstrated co-segregation of the disease. Haplotype analysis showed that the same haplotype was carried by all affected males and obligatory carrier females. Mutation analysis of the proband has revealed a novel nonsense mutation (c.1135C …

Using cDNA microarrays to identify human CD19(+) B cell gene products (ESTs) originated from systemic lupus erythematosus susceptibility loci.

Systemic lupus erythematosus (SLE) is a prototype of autoimmune disease which arises from interactions between susceptibility genes and envi … cDNA microarray technology to investigate the differential gene expression of CD19(+) B cells with genetic linkage data. Bioinformatics programs served to evidentiate the differentially expressed sequences and the design of the microarray allowed hierarchical clustering of patients and controls. Sequencing allowed the identification of 8 new gene products differ …

Linkage mapping of a novel susceptibility locus for Behçet's disease to chromosome 6p22-23.

OBJECTIVE: The etiology of Behçet's disease is unknown; however, familial aggregation studies indicate a strong genetic background and a complex inheritance model. Association of HLA-B51 with Behçet's disease is regarded as being the strongest evidence of genetic contribution described to date. A low rate of recombination was observed within the telomeric end of the major histocompatibility complex up to the HFE gene, which causes hereditary hemochromatosis. We therefore hypothesized that the telomere of 6p may harbor a susceptibility gene for Behçet's disease. METHODS: A series of 28 multica

Genomewide linkage analysis of celiac disease in Finnish families.

Celiac disease (CD), or gluten-sensitive enteropathy, is a common multifactorial disorder resulting from intolerance to cereal prolamins. The only established genetic susceptibility factor is HLA-DQ, which appears to explain only part of the overall genetic risk. We performed a genomewide scan of CD in 60 Finnish families. In addition to strong evidence for linkage to the HLA region at 6p21.3 (Z(max)>5), suggestive evidence for linkage was found for six other chromosomal regions--1p36, 4p15, 5q31, 7q21, 9p21-23, and 16q12. We further analyzed the three most convincing regions--4p15, 5q31, and

High-Density Linkage Map and Mapping for Sex and Growth-Related Traits of Largemouth Bass (Micropterus salmoides).

The largemouth bass is an important species, and its culture has risen sharply with the surge in fish aquaculture in China. Due to the lack … aits are located in 13 LG regions and have little effect on phenotypic variation. This high-density genetic linkage map will enable the fine-mapping of economic traits and support the future genome assembly of the largemouth bass. Additionally, our study will be useful for future selective culture of largemouth bass and could potentially be used in molecular-assi …

Accuracy of direct mutation testing by TaqMan quantitative polymerase chain reaction for preimplantation genetic diagnosis of recurrent de novo mutations.

OBJECTIVE: To assess the accuracy and allele dropout (ADO) rate of preimplantation genetic testing for monogenic disease (PGT-M) when performing direct mutation testing alone, in the absence of family member-based linkage analysis. DESIGN: Retrospective evaluation of concordance between direct mutation testing using TaqMan quantitative polymerase chain reaction (qPCR) and linkage-based analysis to estimate ADO rates when linkage is unavailable. SUBJECTS: In vitro fertilization (IVF) patients who had their embryos evaluated for PGT-M. EXPOSURE: None. MAIN OUTCOME MEASURES: Mendelian ratio a

Analysis of pedigree data in populations with multiple ancestries: Strategies for dealing with admixture in Caribbean Hispanic families from the ADSP.

Multipoint linkage analysis is an important approach for localizing disease-associated loci in pedigrees. Linkage analysis, however, is sensitive to misspecification of marker allele frequencies. Pedigrees from recently admixed populations are particularly susceptible to this problem because of the challenge of accurately accounting for population structure. Therefore, increasing emphasis on use of multiethnic samples in genetic studies requires reevaluation of best practices, given data currently available. Typical strategies have been to compute allele frequencies from the sample, or to use

Absence of linkage of phonological coding dyslexia to chromosome 6p23-p21.3 in a large family data set.

Previous studies have suggested that a locus predisposing to specific reading disability (dyslexia) resides on chromosome 6p23-p21.3. We investigated 79 families having at least two siblings affected with phonological coding dyslexia, the most common form of reading disability (617 people genotyped, 294 affected), and we tested for linkage with the genetic markers reported to be linked to dyslexia in those studies. No evidence for linkage was found by LOD score analysis or affected-sib-pair methods. However, using the affected-pedigree-member (APM) method, we detected significant evidence for

Suggestion of a major gene for familial febrile convulsions mapping to 8q13-21.

Febrile convulsions affect 2 to 5% of all children under the age of 5 years. These convulsions probably have a variety of causes, but a genetic component has long been recognised. A large and remarkable family is described in which febrile convulsions appear to result from autosomal dominant inheritance at a single major locus. A gene for febrile convulsions was excluded from regions of previously mapped epilepsy genes and extension of exclusion mapping, using microsatellite markers, to the entire genome implied that a locus on chromosome 8q13-21 may be involved. Linkage analysis of markers on

Absence of linkage of hereditary motor and sensory neuropathy type I to chromosome 1 markers.

Although one large family with hereditary motor and sensory neuropathy (HMSN) type I that showed linkage to the Duffy blood group (FY) on chromosome 1 has previously been reported, we have failed to find evidence for such linkage after examining 14 markers from chromosome 1 in 12 pedigrees. We have excluded linkage between HMSN I and FY up to theta = 0.15 (lod = -3.01) and also between HMSN I and markers flanking FY; amylase (AMY), polymorphic urinary mucin (PUM), serum amyloid protein (APCS), and alpha-spectrin (SPTA). We have excluded HMSN I from 70 cM around this linkage group. Other marker

Анализ многократной миеломы (ММ) и Моноклональной гаммопатии неопределенных знаков (MGUS)

История семьи является известным фактором риска для множественной миеломы (ММ) и ее предшественника, моноколональной гаммопатии неопределённого значения (МГУС). Предыдущие исследования в рамках всей ассоциации генома (ОСГ) выявили 35 общие loci, связанные с риском MM и 21 связанные с MGS. Цель этого исследования заключалась в выявлении менее распространенных и редких генетических loci, предвосхищающих MM/MGUS, путем проведения анализа последовательности связей на основе целых экспозиций (WES).МЕТОДЫ: Мультиточечный анализ связей был проведен с использованием многоточечного двигателя быстрого с

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… Genetic linkage mapping of chromosome 17 markers and neurofibromatosis type I Am. J. Hum. Genet. 1989 44 25 29 2491777 PMC1715473 46. Wooster R. Neuhausen S.L. Mangion J. Quirk Y. Ford D. Collins N. Nguyen K. Seal S. Tran T. Averill D. …

A genome-wide analysis in consanguineous families reveals new chromosomal loci in specific language impairment (SLI).

Language is a uniquely human ability, and failure to attain this ability can have a life-long impact on the affected individuals. This is particularly true for individuals with specific language impairment (SLI), which is defined as an impairment in normal language development in the absence of any other developmental disability. Although SLI displays high heritability, family-based linkage studies have been hampered by an unclear mode of Mendelian segregation, variable disease penetrance, and heterogeneity of diagnostic criteria. We performed genome-wide parametric linkage analysis and homozy

Linkage disequilibrium block single-nucleotide polymorphisms in FTO alpha ketoglutarate dependent dioxygenase gene inference with breast cancer and Type II diabetes in Pakistani female population.

Breast Cancer and Diabetes Mellitus are top ranked non-communicable life threatening diseases concerned in South Asia. The growing scientific clues witness the involvement of genetic variations which readily serve as risk factors for the disease onset. Comprehending the association of genetic predictors and risk factors in the conserved genome regions can help reveal underlying disease genetics and identify the sustained druggable targets. The present study aims to identify discrete inference of FTO alpha-ketoglutarate dependent dioxygenase gene linkage disequilibrium block SNPs rs9940128 and

Positive selection alone is sufficient for whole genome differentiation at the early stage of speciation process in the fall armyworm.

BACKGROUND: The process of speciation involves differentiation of whole genome sequences between a pair of diverging taxa. In the absence of … ifferentiated sequences (FST > 0). We found that the combined effect of mild positive selection and genetic linkage to selectively targeted loci are responsible for the genomic differentiation. However, a single event of very strong positive selection appears not to be responsible for genomic differentiation. The contribution of chromosomal inversions or tight ge …

Association mapping by pooled sequencing identifies TOLL 11 as a protective factor against Plasmodium falciparum in Anopheles gambiae.

BACKGROUND: The genome-wide association study (GWAS) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based GWAS essentially unfeasible at realistic sample size and marker density. METHODS: We designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. We established founder colo