Paterson, RL and De Roach, JN and McLaren, TL and Hewitt, AW and Hoffmann, L and Lamey, TM, Application of a high-throughput genotyping method for loci exclusion in non-consanguineous Australian pedigrees with autosomal recessive retinitis pigmentosa, Molecular Vision, 18 pp. 2043-2052. ISSN 1090-0535 (2012) [Refereed Article]
METHODS: DNA samples were collected from 59 individuals affected with arRP and 74 unaffected family members from 31 Australian families. Five to six SNPs were genotyped for 28 genes known to cause arRP or the related disease Leber congenital amaurosis (LCA). Cosegregation analyses were used to exclude possible causative genes from each of the 31 families. Bidirectional sequencing was used to identify disease-causing mutations in prioritized genes that were not excluded with cosegregation analyses.
RESULTS: Two families were excluded from analysis due to identification of false paternity. An average of 28.9% of genes were excluded per family when only one affected individual was available, in contrast to an average of 71.4% or 89.8% of genes when either two, or three or more affected individuals were analyzed, respectively. A statistically significant relationship between the proportion of genes excluded and the number of affected individuals analyzed was identified using a multivariate regression model (p<0.0001). Subsequent DNA sequencing resulted in identification of the likely disease-causing gene as CRB1 in one family (c.2548 G>A) and USH2A in two families (c.2276 G>T).
CONCLUSIONS: This study has shown that SNP genotyping cosegregation analysis can be successfully used to refine and expedite the genetic characterization of arRP in a non-consanguineous population; however, this method is effective only when DNA samples are available from more than one affected individual.
|Item Type:||Refereed Article|
|Research Division:||Medical and Health Sciences|
|Research Group:||Ophthalmology and Optometry|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Hearing, Vision, Speech and Their Disorders|
|Author:||Hewitt, AW (Dr Alex Hewitt)|
|Deposited By:||Medicine (Discipline)|
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