Fine mapping of an imprinted gene for familial nonchromaffin paragangliomas, on chromosome 11q23
AMERICAN JOURNAL OF HUMAN GENETICS
Authors: Baysal, BE; Farr, JE; Rubinstein, WS; Galus, RA; Johnson, KA; Aston, CE; Myers, EN; Johnson, JT; Carrau, R; Kirkpatrick, SJ; Myssiorek, D; Singh, D; Saha, S; Gollin, SM; Evans, GA; James, MR; Richard, CW
Abstract
Hereditary nonchromaffin paragangliomas (PGL; glomus tumors; MIM 168000) are mostly benign, slow-growing tumors of the head and neck region, inherited from carrier fathers in an autosomal dominant fashion subject to genomic imprinting. Genetic linkage analysis in two large, unrelated Dutch families assigned PGL loci to two regions of chromosome 11, at 11q23 (PGL1) and 11q13.1 (PGL2). We ascertained a total of 11 North American PGL families and confirmed maternal imprinting (inactivation). In three of six families, linkage analysis provided evidence of linkage to the PGL1 locus at 11q23. Recombinants narrowed the critical region to an similar to 4.5-Mb interval flanked by markers D11S1647 and D11S622. Partial allelic loss of strictly maternal origin was detected in 5 of 19 tumors. The greatest degree of imbalance was detected at 11q23, distal to D11S1327 and proximal to CD3D. Age at onset of symptoms was significantly different between fathers and children (Wilcoxon rank-sum test, P < .002). Affected children had an earlier age at onset of symptoms in 39 of 57 father-child pairs (chi(2) = 7.74, P < .006). However, a more conservative comparison of the number of pairs in which a child had greater than or equal to 5 years earlier age at onset (n = 33) vis-a-vis that of complementary pairs (n = 24) revealed no significant difference (chi(2) = 1.42, P > .2). Whether these data represent genetic anticipation or ascertainment bias can be addressed only by analysis of a larger number of father-child pairs.
CD3D and PRKCQ work together to discriminate between B-cell and T-cell acute lymphoblastic leukemia
COMPUTERS IN BIOLOGY AND MEDICINE
Authors: Ma, Dongli; Zhong, Shan; Liu, Xiaorong; Mai, Huirong; Mai, Guoqin; Xu, Cheng; Zhou, Fengfeng
Abstract
Different therapeutic methods have been developed for the B-cell and T-cell subtypes of acute lymphoblastic leukemia (ALL). The identification of molecular biomarkers that can accurately discriminate between B-cell and T-cell ALLs will facilitate the quick determination of therapeutic plans, as well as reveal the intrinsic mechanisms underlining the two different ALL subtypes. This study computationally screened the high-throughput transcriptome dataset for multiple candidate biomarkers and verified their discrimination abilities in an independent sample set using quantitative real-time polymerase chain reaction (PCR) technology. Both technologies suggest that the two genes CD3D and PKRCQ together provided a good model for classification of B-cell and T-cell ALLs, whereas the individual genes did not show consistent discrimination between the two ALL subtypes. Supplementary material is available at http://healthinformaticslab.org/supp/. (C) 2016 Elsevier Ltd. All rights reserved.