Molecular characterization of ovine GM1 gangliosidosis

Walker, Kristen

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https://hdl.handle.net/2142/42257 Copy

Description

Title

Molecular characterization of ovine GM1 gangliosidosis

Author(s)

Walker, Kristen

Issue Date

2013-02-03T19:29:24Z

Director of Research (if dissertation) or Advisor (if thesis)

Beever, Jonathan E.

Department of Study

Animal Sciences

Discipline

Animal Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• recessive
• ovine
• sheep
• ganglioside
• gangliosidosis
• galactosidase
• association mapping

Abstract

Ovine GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder. Affected lambs are born relatively normal, however at approximately four months of age they begin exhibiting severe neurological symptoms. Pathology progresses rapidly in affected lambs ultimately resulting in death by five to six months of age. In humans and other species, mutations in the β-galactosidase (GLB1) gene are responsible for similar disease phenotypes. The production of non-functional β-galactosidase results in a buildup of GM1 gangliosides and other terminally linked galactose-containing molecules in the brain and visceral tissues. Using the Illumina® OvineSNP50 BeadChip platform, seven affected and ten unaffected animals were genotyped and a genome wide association analysis was performed using PLINK. A significant association was detected for multiple SNPs on OAR19; further investigation showed this area was orthologous to HSA3 containing GLB1. Sequence analysis revealed a G to T nucleotide transversion in exon six of ovine GLB1 resulting in a nonsynonymous cysteine to phenylalanine (Cys229Phe) amino acid substitution. A PCR-RFLP assay using AciI restriction enzyme was designed for genotyping lambs. To date, 1664 animals have been genotyped using the DNA-based diagnostic and all affected lambs were homozygous for this mutation. Conversely, individuals with normal phenotypes were either heterozygous or homozygous for the alternative allele. Affected lambs will be used as an animal model to further explore the disease and potentially identify therapies for humans.

Graduation Semester

2012-12

Permalink

http://hdl.handle.net/2142/42257

Copyright and License Information

Copyright 2012 Kristen Walker

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