Family studies in multiple sclerosis: HLA haplotypes of affected sib-pairs

1984 ◽  
Vol 234 (1) ◽  
pp. 5-7 ◽  
Author(s):  
H. J. Mayer-Rienecker ◽  
S. Wegener ◽  
B. Hitzschke
Keyword(s):  
Multiple Sclerosis ◽  
Family Studies ◽  
Hla Haplotypes ◽  
Affected Sib Pairs ◽  
Sib Pairs

Multiple sclerosis susceptibility and the X chromosome

2007 ◽  
Vol 13 (7) ◽  
pp. 856-864 ◽  
Author(s):  
BM Herrera ◽  
MZ Cader ◽  
DA Dyment ◽  
JT Bell ◽  
GC DeLuca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
X Chromosome ◽  
Complex Trait ◽  
Female Gender ◽  
Complex Interactions ◽  
Parent Of Origin ◽  
Affected Sib Pairs ◽  
Significant Linkage ◽  
Origin Effect ◽  
Sib Pairs

Multiple sclerosis (MS) is a chronic autoimmune complex trait with strong evidence for a genetic component. A female gender bias is clear but unexplained and a maternal parent-of-origin effect has been described. X-linked transmission of susceptibility has been previously proposed, based on pedigree, association and linkage studies. We genotyped 726 relative pairs including 552 affected sib-pairs for 22 X-chromosome microsatellite markers and a novel dataset of 195 aunt-uncle/niece-nephew (AUNN) affected pairs for 18 markers. Parent-of-origin effects were explored by dividing AUNN families into likely maternal and paternal trait transmission. For the sib-pair dataset we were able to establish exclusion at a λ s = 1.9 for all markers using an exclusion threshold of LOD ≤—2. Similarly for the AUNN dataset, we established exclusion at λAV = 1.9. For the combined dataset we estimate exclusion of λ = 1.6. We did not identify significant linkage in either the sib-pairs or the AUNN dataset nor when datasets were stratified for the presence/absence of the HLA-DRB1*15 allele or for paternal or maternal transmission. This comprehensive scrutiny of the X-chromosome suggests that it is unlikely to harbour an independent susceptibility locus or one which interacts with the HLA. Complex interactions including epigenetic ones, and masking by balanced polymorphisms are mechanisms not excluded by the approach taken. Multiple Sclerosis 2007; 13 : 856—864. http://msj.sagepub.com

HLA-DW2, viral immunity and family studies in multiple sclerosis

1977 ◽  
Vol 32 (2) ◽  
pp. 153-167 ◽  
Author(s):  
G.J Stewart ◽  
A Basten ◽  
J Guinan ◽  
H.V Bashir ◽  
J Cameron ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family Studies ◽  
Viral Immunity

scholarly journals High Resolution Haplotype Analyses of Classical HLA Genes in Families With Multiple Sclerosis Highlights the Role of HLA-DP Alleles in Disease Susceptibility

2021 ◽  
Vol 12 ◽  
Author(s):  
Kazutoyo Osoegawa ◽  
Lisa E. Creary ◽  
Gonzalo Montero-Martín ◽  
Kalyan C. Mallempati ◽  
Sridevi Gangavarapu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Statistical Significance ◽  
Hla Class I ◽  
Protective Effects ◽  
Genetic Associations ◽  
Hla Alleles ◽  
Hla Genes ◽  
Haplotype Allele ◽  
Family Based ◽  
Hla Haplotypes

Multiple sclerosis (MS) susceptibility shows strong genetic associations with HLA alleles and haplotypes. We genotyped 11 HLA genes in 477 non-Hispanic European MS patients and their 954 unaffected parents using a validated next-generation sequencing (NGS) methodology. HLA haplotypes were assigned unequivocally by tracing HLA allele transmissions. We explored HLA haplotype/allele associations with MS using the genotypic transmission disequilibrium test (gTDT) and multiallelic TDT (mTDT). We also conducted a case-control (CC) study with all patients and 2029 healthy unrelated ethnically matched controls. We performed separate analyses of 54 extended multi-case families by reviewing transmission of haplotype blocks. The haplotype fragment including DRB5*01:01:01~DRB1*15:01:01:01 was significantly associated with predisposition (gTDT: p < 2.20e-16; mTDT: p =1.61e-07; CC: p < 2.22e-16) as reported previously. A second risk allele, DPB1*104:01 (gTDT: p = 3.69e-03; mTDT: p = 2.99e-03; CC: p = 1.00e-02), independent from the haplotype bearing DRB1*15:01 was newly identified. The allele DRB1*01:01:01 showed significant protection (gTDT: p = 8.68e-06; mTDT: p = 4.50e-03; CC: p = 1.96e-06). Two DQB1 alleles, DQB1*03:01 (gTDT: p = 2.86e-03; mTDT: p = 5.56e-02; CC: p = 4.08e-05) and DQB1*03:03 (gTDT: p = 1.17e-02; mTDT: p = 1.16e-02; CC: p = 1.21e-02), defined at two-field level also showed protective effects. The HLA class I block, A*02:01:01:01~C*03:04:01:01~B*40:01:02 (gTDT: p = 5.86e-03; mTDT: p = 3.65e-02; CC: p = 9.69e-03) and the alleles B*27:05 (gTDT: p = 6.28e-04; mTDT: p = 2.15e-03; CC: p = 1.47e-02) and B*38:01 (gTDT: p = 3.20e-03; mTDT: p = 6.14e-03; CC: p = 1.70e-02) showed moderately protective effects independently from each other and from the class II associated factors. By comparing statistical significance of 11 HLA loci and 19 haplotype segments with both untruncated and two-field allele names, we precisely mapped MS candidate alleles/haplotypes while eliminating false signals resulting from ‘hitchhiking’ alleles. We assessed genetic burden for the HLA allele/haplotype identified in this study. This family-based study including the highest-resolution of HLA alleles proved to be powerful and efficient for precise identification of HLA genotypes associated with both, susceptibility and protection to development of MS.

Genetic segregation of multiple sclerosis and histocompatibility (HLA) haplotypes

1979 ◽  
Vol 222 (2) ◽  
pp. 67-74 ◽  
Author(s):  
M. Alter ◽  
J. Quevedo
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Segregation ◽  
Hla Haplotypes

A Robust Identity-by-Descent Procedure Using Affected Sib Pairs: Multipoint Mapping for Complex Diseases

2000 ◽  
Vol 51 (1-2) ◽  
pp. 64-78 ◽  
Author(s):  
Kung-Yee Liang ◽  
Yen-Feng Chiu ◽  
Terri H. Beaty
Keyword(s):  
Complex Diseases ◽  
Identity By Descent ◽  
Affected Sib Pairs ◽  
Sib Pairs ◽  
Multipoint Mapping

scholarly journals Linkage analysis of a candidate region in Scandinavian sib pairs with multiple sclerosis reveals linkage to chromosome 17q

2000 ◽  
Vol 1 (7) ◽  
pp. 456-459 ◽  
Author(s):  
F Larsen ◽  
A Oturai ◽  
LP Ryder ◽  
HO Madsen ◽  
J Hillert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Linkage Analysis ◽  
Candidate Region ◽  
Chromosome 17Q ◽  
Sib Pairs

scholarly journals Gene‐based and pathway‐based testing for rare‐variant association in affected sib pairs

2020 ◽  
Vol 44 (4) ◽  
pp. 368-381
Author(s):  
Razvan G. Romanescu ◽  
Jessica Green ◽  
Irene L. Andrulis ◽  
Shelley B. Bull
Keyword(s):  
Rare Variant ◽  
Rare Variant Association ◽  
Affected Sib Pairs ◽  
Sib Pairs

scholarly journals Incorporating quantitative variables into linkage analysis using affected sib pairs

2007 ◽  
Vol 1 (S1) ◽  
Author(s):  
Yen-Feng Chiu ◽  
Jeng-Min Chiou ◽  
Yi-Shin Chen ◽  
Hui-Yi Kao ◽  
Fang-Chi Hsu
Keyword(s):  
Linkage Analysis ◽  
Affected Sib Pairs ◽  
Sib Pairs
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