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

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.

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 immunopathic trait and HLA-DR(2)15 as independent risk factors in multiple sclerosis

2007 ◽  
Vol 13 (4) ◽  
pp. 441-445 ◽  
Author(s):  
M. Callander ◽  
S. Haghighi ◽  
A.-M. Landtblom ◽  
C.E. Ahlgren ◽  
S.I. Nilsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Susceptibility Gene ◽  
Hla Dr ◽  
Healthy Siblings ◽  
Independent Risk Factors ◽  
Oligoclonal Igg ◽  
Hla Haplotypes ◽  
Oligoclonal Igg Bands

We analysed HLA haplotypes in pairs of 78 sporadic multiple sclerosis (MS) patients and 78 healthy siblings. The presence of 2 oligoclonal IgG bands, detected by immunoblotting of the cerebrospinal fluid in healthy siblings, has previously been defined as MS immunopathic trait (MSIT), based on a cut-off derived from healthy unrelated volunteers. The frequency of MSIT was 17.9% (n=14/78 siblings). The HLA-DR(15)2 allelle was present in 21.4% (n=3/14) of the siblings with MSIT, in 40.6% (n =26/64) of the siblings without MSIT, and in 59% (n =46/78) of the patients with clinically-definite (CD) MS. The distribution of zero, one or two HLA-DR(2)15 alleles was significantly skewed towards a lower allelle count in the siblings with MSIT compared with the group of unrelated siblings with MS (P=0.002), and also lower than their related siblings with MS (P=0.1). These results suggest that the MS susceptibility gene, HLA-DR(2)15 type, does not induce MSIT, and conceivably these are two separate risk factors in the development of MS. The effect of HLA-DR(2)15 and MSIT in sporadic MS appears to be synergistic. Multiple Sclerosis 2007; 13: 441-445. http://msj.sagepub.com

HLA Haplotypes in Families With High Frequency of Multiple Sclerosis

1976 ◽  
Vol 33 (12) ◽  
pp. 808-812 ◽  
Author(s):  
J.-E. Olsson ◽  
E. Moller ◽  
H. Link
Keyword(s):  
Multiple Sclerosis ◽  
High Frequency ◽  
Hla Haplotypes

Analysis of extended HLA haplotypes in multiple sclerosis and narcolepsy families confirms a predisposing effect for the class I region in Tasmanian MS patients

2007 ◽  
Vol 59 (3) ◽  
pp. 177-186 ◽  
Author(s):  
Justin P. Rubio ◽  
Melanie Bahlo ◽  
Jim Stankovich ◽  
Rachel K. Burfoot ◽  
Laura J. Johnson ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Class I ◽  
Hla Haplotypes ◽  
Class I Region

Population frequency of HLA haplotypes contributes to the prevalence difference of multiple sclerosis in Ireland

2005 ◽  
Vol 252 (10) ◽  
pp. 1245-1248 ◽  
Author(s):  
C. McGuigan ◽  
C. Dunne ◽  
J. Crowley ◽  
R. Hagan ◽  
G. Rooney ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Population Frequency ◽  
Prevalence Difference ◽  
Hla Haplotypes

Microglia-derived macrophages in early multiple sclerosis plaques

1996 ◽  
Vol 22 (3) ◽  
pp. 207-215 ◽  
Author(s):  
H. Li ◽  
M. L. Cuzner ◽  
J. Newcombe
Keyword(s):  
Multiple Sclerosis
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