Quantitative trait loci for human muscle strength: linkage analysis of myostatin pathway genes

2005 ◽  
Vol 22 (3) ◽  
pp. 390-397 ◽  
Author(s):  
W. Huygens ◽  
M. A. I. Thomis ◽  
M. W. Peeters ◽  
J. Aerssens ◽  
R. Vlietinck ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Linkage Analysis ◽  
Quantitative Trait ◽  
Single Point ◽  
Linkage Study ◽  
Human Muscle ◽  
Lod Score ◽  
Strong Inhibitor ◽  
Myostatin Gene ◽  
Multipoint Linkage

This study reports the results of a multipoint linkage study that aims to unravel the genetic basis of muscle strength and muscle mass in humans. Myostatin ( GDF8) is known to be a strong inhibitor of muscle growth in animals. However, studies examining human myostatin polymorphisms are rare and are limited to the GDF8 gene itself. Here, the contribution to isometric and concentric knee strength of nine key proteins involved in the myostatin pathway is studied in a nonparametric multipoint linkage analysis by means of a variance components and regression method. A sample of 367 healthy young male siblings was phenotyped on an isokinetic dynamometer and genotyped for markers of the myostatin pathway genes. Three of the loci were found significantly linked with a quantitative trait locus (QTL) for knee muscle strength. First, D13S1303 showed replication of an explorative single-point linkage study with a maximum LOD score of 2.7 ( P = 0.0002). Second, maximum LOD scores of 3.4 ( P = 0.00004) and 3.3 ( P = 0.00005) were observed for markers D12S1042 and D12S85, respectively, at 12q12–14. Finally, marker D12S78 showed an LOD score of 2.7 at 12q22–23. We conclude that several genes involved in the myostatin pathway, but not the myostatin gene itself, are important QTLs for human muscle strength. An additional set of valuable candidate genes that were not part of the myostatin pathway was found in the chromosome 12 and 13 genomic regions.

scholarly journals Genetic Analysis of a Large Family with Migraine, Vertigo, and Motion Sickness

2019 ◽  
Vol 46 (5) ◽  
pp. 512-517 ◽  
Author(s):  
Leema Reddy Peddareddygari ◽  
Phillip D. Kramer ◽  
Philip A. Hanna ◽  
Mark A. Levenstien ◽  
Raji P. Grewal
Keyword(s):  
Linkage Analysis ◽  
Motion Sickness ◽  
Autosomal Recessive ◽  
Large Family ◽  
American Family ◽  
Chromosome 4 ◽  
Microsatellite Repeat ◽  
Lod Score ◽  
Genome Wide ◽  
Multipoint Linkage

ABSTRACT:Background: Migraine is a common disorder most typically presenting as headache and often associated with vertigo and motion sickness. It is a genetically complex condition with multiple genes ultimately contributing to the predisposition and development of this episodic neurological disorder. We identified a large American family of 29 individuals of which 17 members suffered from at least one of these disorders, migraine, vertigo, or motion sickness. Many of these individuals suffered from several simultaneously. We hypothesized that vertigo and motion sickness may involve genes that are independent to those directly contributing to migraine susceptibility. Methods: Genome-wide linkage analysis performed using 400 microsatellite repeat markers spaced at 10 cM throughout the genome. The members of this family were phenotyped for each condition, migraine, vertigo, and motion sickness and analyzed separately. Statistical analysis was performed using two-point and multipoint linkage analysis employing a number of models including autosomal recessive or dominant patterns of inheritance with high and low genetic penetrance. Results: We identified a novel locus for migraine, 9q13-q22 (maximum two-point logarithm of odds [LOD] score-2.51). In addition, there are suggestive LOD scores that localize to different chromosomes for each phenotype; vertigo (chromosome 18, LOD score of 1.82) and motion sickness (chromosome 4, LOD score of 2.09). Conclusions: Our analysis supports our hypothesis that the migraine-associated vertigo and motion sickness may involve distinct susceptibility genes.

Heritability and Whole Genome Linkage of Pulse Pressure in Chinese Twin Pairs

2012 ◽  
Vol 15 (6) ◽  
pp. 759-766 ◽  
Author(s):  
Wengjie Jiang ◽  
Dongfeng Zhang ◽  
Zengchang Pang ◽  
Shuxia Li ◽  
Haiping Duan ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Pulse Pressure ◽  
Chinese Population ◽  
Molecular Genetic ◽  
Snp Array ◽  
Heritability Estimate ◽  
Linkage Study ◽  
Chromosome 11 ◽  
Lod Score ◽  
Genome Wide

Elevated pulse pressure is associated with cardiovascular disorders and mortality in various populations. The genetic influence on pulse pressure has been confirmed by heritability estimates using related individuals. Recently, efforts have been made in mapping genes that are linked to the phenotype. We report results on our heritability and linkage study conducted on the Chinese population in mainland China where cardiovascular and cerebrovascular diseases are becoming the leading cause of death. A total of 630 pairs of middle-aged Chinese twins were collected for heritability analysis, from which 63 dizygotic twin pairs were randomly selected for genome-wide linkage analysis using Affymetrix 6.0 SNP array. Regression analysis reconfirmed the significant effects of age, sex, and BMI on pulse pressure. Comparison of twin models suggested the parsimonious AE model as the best model with a heritability estimate of 0.45. Genome-wide non-parametric linkage analysis identified three significant linkage peaks on chromosome 11 (lod score 4.06 at 30.5 cM), chromosome 12 (lod score 3.97 at 100.7 cM), and chromosome 18 (lod score 4.01 at 70.7 cM) with the last two peaks closely overlapping with linkage peaks reported by two American studies. In addition, multiple regions with suggestive linkage were identified with many of them overlapping with published linkage regions. Our results provide both epidemiological and molecular genetic evidence for the genetic dissection of pulse pressure in the Chinese population, which could help in fine mapping and in characterizing genes that are involved in the regulation of pulse pressure.

Multivariate multipoint linkage analysis of quantitative trait loci

1996 ◽  
Vol 26 (5) ◽  
pp. 519-525 ◽  
Author(s):  
Lindon J. Eaves ◽  
Michael C. Neale ◽  
Hermine Maes
Keyword(s):  
Quantitative Trait Loci ◽  
Linkage Analysis ◽  
Quantitative Trait ◽  
Multipoint Linkage Analysis ◽  
Multipoint Linkage ◽  
Trait Loci

A genome wide quantitative trait linkage analysis for serum lipids in type 2 diabetes in an African population

2005 ◽  
Vol 181 (2) ◽  
pp. 389-397 ◽  
Author(s):  
Adebowale A. Adeyemo ◽  
Thomas Johnson ◽  
Joseph Acheampong ◽  
Johnnie Oli ◽  
Godfrey Okafor ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Linkage Analysis ◽  
Quantitative Trait ◽  
Serum Lipids ◽  
African Population ◽  
Quantitative Trait Linkage Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Quantitative Trait Linkage

A linkage study in two families with multiple sclerosis and healthy members with oligoclonal CSF immunopathy

2006 ◽  
Vol 12 (6) ◽  
pp. 723-730 ◽  
Author(s):  
S Haghighi ◽  
O Andersen ◽  
S Nilsson ◽  
L Rydberg ◽  
J Wahlström
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Model ◽  
Single Gene ◽  
Parametric Method ◽  
Linkage Study ◽  
Suggestive Linkage ◽  
Lod Score ◽  
Extended Families ◽  
A Genome ◽  
Reduced Penetrance

We studied two extended families in which not only multiple sclerosis (MS) segregates, but also approximately 18% of the cerebrospinal fluid (CSF) investigated blood relatives have ‘MS immunopathic trait’, an oligoclonal CSF immunopathy similar to that seen in MS, but with no neurological symptoms. Both families fit a genetic model for autosomal dominant inheritance for MS immunopathic trait, although with reduced penetrance in family A. In order to identify genetic factors of importance for the development of MS immunopathic trait, we performed a genome scan using the CHLC/Weber Screening Set (ver 6A), with 285 successful markers, to test the hypothesis that a single gene is causing the MS immunopathic trait in these families. Using a parametric method, we identified regions with suggestive linkage at chromosome 6q12 with a LOD-score of 2.4, putative linkage with LOD-score 1.5 at chromosome 6p21 (HLA region), putative linkage at chromosome 12q24 with a LOD-score of 1.7 and suggestive linkage at chromosome 19q13.2 with a LOD-score of 1.8. The LOD-score at chromosome 19q13.2 increased to 2.2 when only family A was analysed. In family A, all MS patients and two of five individuals with MS immunopathic trait had HLA DRB1*(15) and in family B, all blood relatives had the rare HLA type DRB1*0103, which is associated with other autoimmune diseases. We suggest that DRB1*0103 is a necessary but not sufficient condition for the susceptibility for MS immunopathic trait in this family.

scholarly journals Interval mapping of quantitative trait loci employing correlated trait complexes.

Genetics ◽  
1995 ◽  
Vol 140 (3) ◽  
pp. 1137-1147
Author(s):  
A B Korol ◽  
Y I Ronin ◽  
V M Kirzhner
Keyword(s):  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Interval Mapping ◽  
Simple Relationship ◽  
Broad Sense Heritability ◽  
Lod Score ◽  
Resolution Power ◽  
Mapping Model ◽  
Trait Analysis ◽  
Increasing Function

Abstract An approach to increase the resolution power of interval mapping of quantitative trait (QT) loci is proposed, based on analysis of correlated trait complexes. For a given set of QTs, the broad sense heritability attributed to a QT locus (QTL) (say, A/a) is an increasing function of the number of traits. Thus, for some traits x and y, H(xy)2(A/a) > or = H(x)2(A/a). The last inequality holds even if y does not depend on A/a at all, but x and y are correlated within the groups AA, Aa and aa due to nongenetic factors and segregation of genes from other chromosomes. A simple relationship connects H2 (both in single trait and two-trait analysis) with the expected LOD value, ELOD = -1/2N log(1-H2). Thus, situations could exist that from the inequality H(xy)2(A/a) > or = H(x)2(A/a) a higher resolution is provided by the two-trait analysis as compared to the single-trait analysis, in spite of the increased number of parameters. Employing LOD-score procedure to simulated backcross data, we showed that the resolution power of the QTL mapping model can be elevated if correlation between QTs is taken into account. The method allows us to test numerous biologically important hypotheses concerning manifold effects of genomic segments on the defined trait complex (means, variances and correlations).

scholarly journals Pedigree-Based Gene Mapping Supports Previous Loci and Reveals Novel Suggestive Loci in Specific Language Impairment

2020 ◽  
Vol 63 (12) ◽  
pp. 4046-4061
Author(s):  
Erin M. Andres ◽  
Kathleen Kelsey Earnest ◽  
Shelley D. Smith ◽  
Mabel L. Rice ◽  
Muhammad Hashim Raza
Keyword(s):  
Linkage Analysis ◽  
Language Impairment ◽  
Specific Language Impairment ◽  
Suggestive Linkage ◽  
Lod Score ◽  
Specific Language ◽  
Parametric Linkage Analysis ◽  
Genome Wide ◽  
Age Appropriate ◽  
Language Measure

Purpose Specific language impairment (SLI) is characterized by a delay in language acquisition despite a lack of other developmental delays or hearing loss. Genetics of SLI is poorly understood. The purpose of this study is to identify SLI genetic loci through family-based linkage mapping. Method We performed genome-wide parametric linkage analysis in six families segregating with SLI. An age-appropriate standardized omnibus language measure was used to categorically define the SLI phenotype. Results A suggestive linkage region replicated a previous region of interest with the highest logarithm of odds (LOD) score of 2.40 at 14q11.2-q13.3 in Family 489. A paternal parent-of-origin effect associated with SLI and language phenotypes on a nonsynonymous single nucleotide polymorphism (SNP) in NOP9 (14q12) was reported previously. Linkage analysis identified a new SLI locus at 15q24.3-25.3 with the highest parametric LOD score of 3.06 in Family 315 under a recessive mode of inheritance. Suggestive evidence of linkage was also revealed at 4q31.23-q35.2 in Family 300, with the highest LOD score of 2.41. Genetic linkage was not identified in the other three families included in parametric linkage analysis. Conclusions These results are the first to report genome-wide suggestive linkage with a total language standard score on an age-appropriate omnibus language measure across a wide age range. Our findings confirm previous reports of a language-associated locus on chromosome 14q, report new SLI loci, and validate the pedigree-based parametric linkage analysis approach to mapping genes for SLI. Supplemental Material https://doi.org/10.23641/asha.13203218

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