Transmission disequilibrium test in 943 trios multiple sclerosis families.

<p>Legend: Transmission disequilibrium test (TDT); Transmitted (T); Not transmitted (NT); p value (P); p value corrected (Pc).</p

The inheritance of HLA-DRB1*15:02-DQB1*06:01 (*15:02) in the absence of HLA-DRB1*16:01-DQB1*05:02.

<p>Legend: HLA-DRB1*15:02-DQB1*06:01 (*15:02); X includes the positively associated DRB1*03:01-DQB1*02:01, DRB1*13:03-DQB1*03:01, DRB1*15:01-DQB1*06:02, DRB1*04:05-DQB1*03:01 and “neutral” haplotypes; p value (P). NA means that offspring genotypes are not possible with parental genotypes.</p

Inheritance of HLA-DRB1*16:01-DQB1*05:02 (16) in the absence of the negatively associated HLA-DRB1*15:02-DQB1*06:0, the positively associated DRB1*03:01-DQB1*02:01, DRB1*13:03-DQB1*03:01, DRB1*15:01-DQB1*06:02 and DRB1*04:05-DQB1*03:01. X = “neutral” haplotypes.

<p>X = all other alleles “neutral” haplotypes.</p><p>Legend: HLA-DRB1*16:01-DQB1*05:02 (16); “neutral” haplotypes(X); p value (P). NA means that offspring genotypes are not possible with parental genotypes.</p

HLA DRB1*-DQB1* genotypes from 943 multiple sclerosis patients and 362 healthy siblings, plus 2829 pseudocontrols obtained from healthy parents of the 943 trio families.

<p>Legend: X = all not associated haplotypes. P values threshold is set at 0.005.</p

Inheritance of HLA-DRB1*16:01-DQB1*05:02 in the absence of the negatively associated HLA-DRB1*15:02-DQB1*06:01.

<p>Legend: HLA-DRB1*16:01-DQB1*05:02 (16); X includes the positively associated DRB1*03:01-DQB1*02:01, DRB1*13:03-DQB1*03:01, DRB1*15:01-DQB1*06:02, DRB1*04:05-DQB1*03:01 and “neutral” haplotypes; p value (P). NA means that offspring genotypes are not possible with parental genotypes.</p

Transmission disequilibrium test of the not-transmitted parental haplotype in multiple sclerosis patients carrying (DR3+) or not carrying (DR3−) the HLA-DRB1*03∶01-*02∶01 haplotype.

<p>NA = no mating of this type was available.</p><p>Rare haplotypes belonging to the same haplogroup were grouped together: as *11 were designed *11∶01-02-03-04 -*03∶01, *11∶01-*03∶03-*05∶02 and *11∶04-*06∶03; as *07 were designed *07∶01- *02∶01 and *07∶01-*03∶03; as *13 were designed *13∶01-*06∶03-*03∶03, *13∶02-*05∶01-*05∶031-*06∶02-*06∶04-*06∶05-*06∶09, *13∶05-*03∶01 and *13∶16-DQB1*06∶04; as *04 were designed *04∶01-*03∶01-*03∶02, *04∶02-*03∶02, *04∶03– *03∶01-02-04-05, *04∶04-*03∶02-*04∶02, *04∶05-*02∶01, *04∶05-*03∶02, *04∶06-*03∶02, *04∶07-*03∶01 and *04∶08-*03∶01; as *15 were designed *15∶01-*05∶01-02 and *15∶01-*06∶01-03; as *08 were designed *08∶01-*03∶01-*04∶02, *08∶03-*03∶01 and *08∶04-*03∶01-*04∶02; as *01 were designed *01∶01 *05∶01, *01∶02-*05∶01 and *01∶03- *05∶01.</p

Inheritance of HLA-DRB1*04:05-DQB1*03:01 in the absence of the other predisposing haplotypes DRB1*03:01-DQB1* = 02:01, DRB1*13:03-DQB1*03:01, DRB1*15:01-DQB1*06:01.

<p>Legend: HLA-DRB1*04:05-DQB1*03:01 (4); all other haplotypes (X); p value (P). NA means that offspring genotypes are not possible with parental genotypes.</p

Sequence alignment of the eight MS associated DRB1 alleles.

<p>Only positions with different residues are considered. The first line reports the residue position and the last line the pocket or pockets to which it belongs.</p

Relative predispositional effect: the overall frequency distribution of all haplotypes at the DRB1-DQB1 loci in MS patients (n = 2,555) compared with the distribution in controls (N = 1,365).

<p>DRB1-DQB1 haplotypes in MS patients (col.1), the number observed (col. 2) and expected from controls on the basis of the assumption that there were no differential predispositional effects on the DRB1-DQB1 haplotypes (col. 3), and the contribution of each haplotype to the overall <b>χ</b>2 (col.4). The overall <b>χ</b>2 distribution was considered statistically significant at P<0.001 (col. 5).</p><p>Rare haplotypes belonging to the same haplogroup were grouped together: as *04 were designed *04∶01-*03∶01-*03∶02, *04∶02-*03∶02, *04∶03– *03∶01-02-04-05, *04∶04-*03∶02-*04∶02, *04∶05-*02∶01, *04∶05-*03∶02, *04∶06-*03∶02, *04∶07-*03∶01 and *04∶08-*03∶01; as *08 were designed *08∶01-*03∶01-*04∶02, *08∶03-*03∶01 and *08∶04-*03∶01-*04∶02.</p

Multiple Sequence alignments of the predisposing and protective alleles considered in the study, with only variable amino acid residues reported, for the three DQB1 alleles (*06:01,*05:02,*06:02).

<p>Multiple Sequence alignments of the predisposing and protective alleles considered in the study, with only variable amino acid residues reported, for the three DQB1 alleles (*06:01,*05:02,*06:02).</p