beta-Thalassemia pathogenic variants in a cohort of children from the East African coast
MOLECULAR GENETICS & GENOMIC MEDICINE
Authors: Macharia, Alexander W.; Mochamah, George; Uyoga, Sophie; Ndila, Carolyne M.; Nyutu, Gideon; Tendwa, Metrine; Nyatichi, Emily; Makale, Johnstone; Ware, Russell E.; Williams, Thomas N.
Abstract
Background beta-Thalassemia is rare in sub-Saharan Africa. Previous studies have suggested that it is limited to specific parts of West Africa. Based on hemoglobin A(2) (HbA(2)) concentrations measured by HPLC, we recently speculated that beta-thalassemia might also be present on the East African coast of Kenya. Here, we follow this up using molecular methods. Methods We used raised hemoglobin A(2) (HbA(2)) values (> 4.0% of total Hb) to target all HbAA members of a cohort study in Kilifi, Kenya, for HBB sequencing for beta-thalassemia (n = 99) together with a sample of HbAA subjects with lower HbA(2) levels. Because HbA(2) values are artifactually raised in subjects carrying sickle hemoglobin (HbS) we sequenced all participants with an HPLC pattern showing HbS without HbA (n = 116) and a sample with a pattern showing both HbA and HbS. Results Overall, we identified 83 carriers of four separate beta-thalassemia pathogenic variants: three beta(0)-thalassemia [CD22 (GAA -> TAA), initiation codon (ATG -> ACG), and IVS1-3MODIFIER LETTER PRIME end del 25bp] and one beta(+)-thalassemia pathogenic variants (IVS-I-110 (G -> A)). We estimated the minimum allele frequency of all variants combined within the study population at 0.3%. Conclusions beta-Thalassemia is present in Kilifi, Kenya, an observation that has implications for the diagnosis and clinical care of children from the East Africa region.
Siglecs: A journey through the evolution of sialic acid-binding immunoglobulin-type lectins
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
Authors: Bornhoefft, Kim F.; Goldammer, Tom; Rebl, Alexander; Galuska, Sebastian P.
Abstract
Siglecs (sialic acid-binding immunoglobulin-type lectins) are a family of immune regulatory receptors predominantly found on the cells of the hematopoietic system. A V-set Ig-like domain mediates the recognition of different sialylated glycoconjugates, which can lead to the activation or inhibition of the immune response, depending on the involved Siglecs. Siglecs are categorized into two subgroups: one including all CD33-related Siglecs and the other consisting of Siglec-1 (Sialoadhesin), Siglec-2 (CD22), Siglec-4 (myelin-associated glycoprotein, MAG) and Siglec-15. In contrast to the members of the CD33-related Siglecs, which share similar to 50-99% sequence identity, Siglecs of the other subgroup show quite low homology (approximately 25-30% sequence identity). Based on the published sequences and functions of Siglecs, we performed phylogenetic analyses and sequence alignments to reveal the conservation of Siglecs throughout evolution. Therefore, we focused on the presence of Siglecs in different classes of vertebrates (fishes, amphibians, birds, reptiles and mammals), offering a bridge between the presence of different Siglecs and the biological situations of the selected animals. (C) 2018 The Authors. Published by Elsevier Ltd.