Family Study Analysis Research Articles

P068 The novel recombinant HLA-A*11:271 story: Serology to the rescue of the misnomenclature

Aim The wide spread use of NGS for HLA typing has resulted in exponential growth of novel alleles reported to the IMGT. However, the majority of these novel alleles have not been serologically characterized which has significant clinical implications in solid organ and HCT, particularly pertaining to assignment of donor specific HLA antibodies. Methods The identified novel allele had been originally and unsuccessfully tested by rSSOP, SSP, Sanger SBT and Real-Time PCR. Subsequently, the sample was tested by NGS using Mia Fora reagents and analysis software (Immucor). The subject was redrawn for serologic typing using Terasaki trays (One Lambda). A family study analysis was conducted to determine the segregation of the novel allele carrying haplotype by descent. Results With the exception of NGS, none of the molecular methods produced a result of the A locus. NGS revealed a novel HLA-A allele that appears to result from a recombination between A*11:01:01:01 (ex 1 and partial ex 2) & A:01:01:01 (starting from ex 2) as depicted in the figure of the nucleotide and amino acid partial sequence alignments and the NGS coverage plot. The Mia Fora software assigned the HLA A locus typing as A*33:03:01 and the second allele as novel with the closest reference allele match as A*01:01:01:01. The haplotype assignment function of Mia Fora identified the 2 haplotypes of the subject carrying the novel allele which was confirmed by a family study. The novel allele was confirmed by NGS using TruSight HLA typing kit (Illumina) and submitted to IMGT and assigned the name A*11:271. Serological typing was performed and showed positive reactions with 2 operationally monospecific A1 antisera and one polyspecific (A1 & A36) sera, but with neither of the 2 operationally monospecific A11 antisera on the typing tray. Download : Download high-res image (465KB) Download : Download full-size image Conclusions This report presents a cautionary note that in the absence of serological characterization of HLA alleles, the current IMGT nomenclature may not reflect the clinically relevant antigen specificity of these alleles.

Comorbidity between dysthymic and major depressive disorders: A family study analysis

There is an extremely high rate of comorbidity between Dysthymic Disorder (DD) and Major Depressive Disorder (MDD). We used family study data to test four competing models of the relationship between DD, MDD, and comorbid DD/MDD: (1) DD, MDD, and DD/MDD are all variants of a single condition; (2) MDD and DD/MDD are similar, but differ from DD; (3) DD and DD/MDD are similar, but differ from MDD; and (4) all three conditions are distinct disorders. Subjects were the first-degree relatives of 22 outpatients with DD ( n=103), 45 outpatients with MDD ( n=207), 75 outpatients with comorbid DD/MDD ( n=343), and 45 normal controls ( n=229). Best-estimate diagnoses of relatives were derived using direct and family history interviews. Relatives of patients with DD and comorbid DD/MDD exhibited significantly higher rates of DD than relatives of patients with MDD and normal probands. The rate of comorbid DD/MDD was significantly higher in the relatives of patients with DD/MDD than the relatives of normal probands. Finally, the relatives of patients with MDD and comorbid DD/MDD exhibited significantly higher rates of MDD than the relatives of normal controls. Although none of the models received unambiguous support, some were more plausible than others.