Journal article

Genome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand

Nopasak Phasukkijwatana, Bussaraporn Kunhapan, Jim Stankovich, Wanicha L Chuenkongkaew, Russell Thomson, Timothy Thornton, Melanie Bahlo, Taisei Mushiroda, Yusuke Nakamura, Surakameth Mahasirimongkol, Aung Win Tun, Chatchawan Srisawat, Chanin Limwongse, Chayanon Peerapittayamongkol, Thanyachai Sura, Wichit Suthammarak, Patcharee Lertrit

Human Genetics | SPRINGER | Published : 2010


Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P 2 in 10 of 16 allele sharing models tested) was then expanded to in..

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University of Melbourne Researchers


Awarded by Thailand Research Fund (TRF)

Funding Acknowledgements

The genome-wide linkage scan was performed with the assistance of Dr. Kelly Ewen-White in Australian Genome Research Facility (AGRF), Victoria, Australia. SNPs genotyping and all facilities to perform multiplex-PCR-based Invader assay were supported by Laboratory for Pharmacogenetics, RIKEN Center for Genomic Medicine, Yokohama, Japan, through the genotyping services supports and fellowships to Thai researchers and institutes executed on DMSc-RIKEN's Center for Genomics Medicine (CGM) Collaboration. We acknowledge Sukanya Wattanapokayakit (DMSc, Thailand) for her assistance on collaboration process and SNPs genotyping at RIKEN. Also we sincerely thank Dr. Briony Patterson for the guidance on bioinformatics analyses and discussions. We are especially grateful to Dr. Komon Luangtrakool, Pattamon Tharaphan, Sarinee Pingsutthiwong, Thitima Sunpachudayan, Benjamas Intharabut, Treenud Suntisiri, Yutthana Joyjinda, Dr. Patchara Nantasri and the ophthalmologists for their great assistance in the field trip, DNA extraction and data manipulation. Finally, we thank all of the patients and families for their wonderful cooperation. This work was supported by the Thailand Research Fund (TRF) grant number BRG4580018 to P. Lertrit and PHD/0031/2546 through the Royal Golden Jubilee Ph.D. Program to N. Phasukkijwatana and P. Lertrit, and by Siriraj Research and Development Fund, Faculty of Medicine Siriraj Hospital, Mahidol University (Grant No. 014(II)/49). The SNPs genotyping and statistical genetics analyses were supported by grants from the Faculty of Medicine Siriraj Hospital, Mahidol University and from the National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand.