False-positive rates in two-point parametric linkage analysis

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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Recent Advances in Gene Mapping of Skin Diseases: Pseudoxanthoma Elasticum: A Satisfying Sibling Study

Journal of Cutaneous Medicine and Surgery ◽

10.1177/120347549900300312 ◽

1999 ◽

Vol 3 (3) ◽

pp. 154-156 ◽

Cited By ~ 5

Author(s):

Sherri J. Bale

Keyword(s):

Linkage Analysis ◽

Autosomal Recessive ◽

Recent Progress ◽

Autosomal Dominant ◽

Skin Diseases ◽

Pseudoxanthoma Elasticum ◽

Molecular Defect ◽

Parametric Linkage Analysis ◽

Affected Sib Pair ◽

Made In

Background: A review of the recent progress made in mapping of the hereditary skin disease pseudoxanthoma elasticum is presented. Methods: Affected sib pair methods, parametric linkage analysis, and linkage heterogeneity tests are reviewed as applied to the effort to identify the location of the pseudoxanthoma elasticum gene. Results: Families segregating either autosomal dominant or autosomal recessive pseudoxanthoma elasticum mapped to chromosome 16p13.1. Conclusion: There is a gene for pseudoxanthoma elasticum on chromosome 16p. The underlying molecular defect remains to be elucidated.

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Multipoint and single point non-parametric linkage analysis with imperfect data

American Journal of Medical Genetics ◽

10.1002/ajmg.b.20069 ◽

2003 ◽

Vol 121B (1) ◽

pp. 89-94 ◽

Cited By ~ 11

Author(s):

Patrick F. Sullivan ◽

Benjamin M. Neale ◽

Michael C. Neale ◽

Edwin van den Oord ◽

Kenneth S. Kendler

Keyword(s):

Linkage Analysis ◽

Single Point ◽

Parametric Linkage Analysis ◽

Imperfect Data ◽

Non Parametric

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Allele-Sharing Methods (Non-parametric Linkage Analysis)

Dictionary of Bioinformatics and Computational Biology ◽

10.1002/9780471650126.dob0016.pub2 ◽

2004 ◽

Author(s):

Mark McCarthy ◽

Steven Wiltshire ◽

Andrew Collins

Keyword(s):

Linkage Analysis ◽

Allele Sharing ◽

Parametric Linkage Analysis ◽

Non Parametric

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Power of non-parametric linkage analysis in mapping genes contributing to human longevity in long-lived sib-pairs

Genetic Epidemiology ◽

10.1002/gepi.10304 ◽

2004 ◽

Vol 26 (3) ◽

pp. 245-253 ◽

Cited By ~ 17

Author(s):

Qihua Tan ◽

J. H. Zhao ◽

I. Iachine ◽

J. Hjelmborg ◽

W. Vach ◽

...

Keyword(s):

Linkage Analysis ◽

Human Longevity ◽

Parametric Linkage Analysis ◽

Sib Pairs ◽

Non Parametric

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Parametric Linkage Analysis Identifies Five Novel Genome-Wide Significant Loci for Familial Lung Cancer

Human Heredity ◽

10.1159/000479028 ◽

2016 ◽

Vol 82 (1-2) ◽

pp. 64-74 ◽

Cited By ~ 1

Author(s):

Anthony M. Musolf ◽

Claire L. Simpson ◽

Mariza de Andrade ◽

Diptasri Mandal ◽

Colette Gaba ◽

...

Keyword(s):

Lung Cancer ◽

Linkage Analysis ◽

Parametric Linkage Analysis ◽

Genome Wide

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No evidence of linkage between 7q33–36 locus (OTSC2) and otosclerosis in seven British Caucasian pedigrees

The Journal of Laryngology & Otology ◽

10.1017/s0022215107000655 ◽

2007 ◽

Vol 121 (12) ◽

pp. 1140-1147 ◽

Cited By ~ 4

Author(s):

F Q Alzoubi ◽

W R Ollier ◽

R T Ramsden ◽

S R Saeed

Keyword(s):

Environmental Factors ◽

Linkage Analysis ◽

Genetic Linkage ◽

Deoxyribonucleic Acid ◽

Chromosome Region ◽

Parametric Linkage Analysis ◽

Linkage Score ◽

Multipoint Linkage ◽

Chromosome Regions ◽

Non Parametric

AbstractBackground:The aetiology of otosclerosis is complex, and probably involves an interaction between genes and environmental factors. Previous studies have revealed genetic linkage with a number of chromosome regions, including position 7q33–36.Aim:To confirm whether linkage exists between otosclerosis and chromosome region 7q33–36.Materials and methods:Seven multiply affected families were ascertained. Deoxyribonucleic acid from members of these families was extracted, and six markers were genotyped to cover a 16 cM region at 7q33–36. Both parametric and non-parametric multipoint linkage analyses were performed.Results:Parametric multipoint linkage analysis excluded any linkage at 7q33–36 (logarithm of odds score <−4.0). Non-parametric linkage analysis also failed to confirm any linkage (non-parametric linkage < 1.66). When tested individually, pedigree four was the only one to show a significant non-parametric linkage score between D7s684 and D7s2513 (non-parametric linkage = 1.96).Conclusion:No linkage was detected between otosclerosis and the 7q33–36 region. This could be explained by the study's lack of power, due to the limited number of families available.

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