New Modes of GPCR Signalling

Identification of a Novel Genetic Locus on Chromosome 8p21.1-q11.23
for Idiopathic Basal Ganglia Calcification
Xiaohua Dai,1# Yong Gao,1# Zhenping Xu,1,2# Xiaoniu Cui,1 Juan Liu,1 Yulei Li,1,2
Haibo Xu,3 Mugen Liu,1 Qing K Wang,1,4,* and Jing Yu Liu 1,*
1Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life
Science and Technology, Center for Human Genome Research, Huazhong University
of Science and Technology, 430074, Wuan, Hubei, P. R. China;2Department of Life
Science and Technique, Xinxiang Medical University, Xinxiang, 453003,
China;3Department of Radiology, Union Hospital of Huazhong University of Science
and Technology, Wuhan, 430074, China;4Department of Molecular Cardiology, Lerner
Research Institute, Cleveland Clinic, Cleveland 44195, USA
#Contributed equally to this work.
Objectives:Idiopathic basal ganglia calcification (IBGC) is a neurodegenerative
disorder that is characterized by basal ganglia and extrabasal ganglia calcification, and
usually inherited in an autosomal dominant pattern. To date, two genetic loci for IBGC
were identified on chromosomes 14q and 2q, but further genetic heterogeneity clearly
exists. Methods: Linkage analysis was used to identify the chromosomal location of the
disease gene.Results: A large five-generation Chinese family from Henan Provience
with an autosomal dominant inheritance, family IBGC have identified and characterized.
Linkage analysis excluded the 14q13 and 2q37 loci and other known related genes with
extrapyramidal disease in the nervous system, including ApoE, Tau, ACT, BChE-K,
APP, PS1, PS2 and VLDL-R. Using the family, significant linkage was identified with
markers on chromosome 8p21.1-q11.23 with a maximum LOD score of 4.10. Fine
mapping defined the new genetic locus within a 25.0 cM region between markers
D8S1809 and D8S1833. Interpretation: Future studies of the candidate genes at the
8p21.1-q11.23 locus may lead to identification of a disease-causing gene with IBGC.
Key Words: Idiopathic basal ganglia calcification (IBGC); Linkage analysis; Genetics;
Calcification; LOD score
*Correspondence to:
Dr. J. Y. Liu, liujy@mail.hust.edu.cn
Dr. Q. K. Wang, qkwng@mail.hust.edu.cn