Elucidation of Pattern of Variation for the Amylase Locus in Type 1 Diabetes Patients

Elucidation of Pattern of Variation for the Amylase Locus in Type 1 Diabetes Patients

Bibliographic Details
Main Author: Rutherford, Andrea Marie
Language:English
Published: The Ohio State University / OhioLINK 2012
Subjects:
Genetics
copy number variation
amylase
type 1 diabetes
genetics
pulsed field gel electrophoresis
segmental duplication
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1337716744
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu13377167442021-08-03T06:05:02Z Elucidation of Pattern of Variation for the Amylase Locus in Type 1 Diabetes Patients Rutherford, Andrea Marie Genetics copy number variation amylase type 1 diabetes genetics pulsed field gel electrophoresis segmental duplication <p>Proper metabolism of food, especially glucose, is vital to an organism’s survival. Failure to metabolize polysaccharides and regulate blood glucose levels are hallmarks of diabetes mellitus. Type 1 diabetes (T1D) is a disease where pancreatic beta cells, producers of the insulin that regulates blood glucose levels, are destroyed by the immune system. Most carbohydrates yield glucose, with starch and glycogen being especially rich in glucose. Starch degradation in humans begins with alpha-amylase, which is responsible for the catalytic hydrolyzation of alpha1,4-glycosidic bonds between glucose monomers in starch. Humans express two forms of alpha-amylase that display high tissue specificity. Pancreatic amylase (encoded by <i>AMY2</i>) is expressed by the cells of the exocrine pancreas. Salivary amylase (encoded by <i>AMY1</i>) is produced in the acinar and intercalated duct cells of the parotid salivary gland.</p> <p>Human amylase genes are one of the first reported instances of copy number variation (CNV) among healthy individuals. Six different genes exist in a cluster on chromosome 1 in the human genome – three salivary genes (<i>AMY1A, 1B</i>, and <i>1C</i>), two pancreatic genes (<i>AMY2A</i> and <i>2B</i>) and one truncated pseudogene (<i>AMYP1</i>). In an effort to explain the diversity of amylase CNV in healthy individuals, Peter Groot developed the following: <i>AMY2B-AMY2A-(AMY1A-AMY1B-AMYP1)</i><sub>n</sub><i>-AMY1C</i>, with n = 0 – 2 copies in a diploid individual. Evidence from other reports, such as the absence of <i>AMY2A</i> in the NCBI Alternative Reference genome, suggests that Groot’s model is not an accurate description of variation at this locus. This thesis focuses on further interrogating the amylase locus in T1D individuals to better understand its pattern of variation.</p> <p>Dot-plot analysis of the amylase locus indicated the presence of four large blocks ranging in size from 64kb to 44kb that share sequence homology. Within these blocks are smaller segments of 7-30kb with sequence similarity. <i>Pme</i>I digests revealed segmental duplications of ~20-50kb increments, implicating these blocks in amylase diversification.</p> <p>Comparisons of <i>Taq</i>I, <i>Pst</i>I, and <i>Pvu</i>II/<i>Psh</i>AI digests revealed variable copy number for all amylase genes in individuals. Individuals with short <i>AMY</i> haplotypes provided further insight into the variation and complexity of the locus. Pancreatic <i>AMY2</i> genes, particularly <i>AMY2A</i> appear to vary in copy number throughout the population. An individual was found to be homozygous deficient for <i>AMY2A</i>. Our T1D population as a whole showed large copy number variation for all amylase genes.</p> <p>In conclusion, the human amylase locus undergoes complex variation that most likely includes alignment of large and smaller segments sharing sequence homology. Further studies on quantitative measures on amylase copy number would provide insights into the pattern of variation in health and disease.</p> 2012-06-22 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1337716744 http://rave.ohiolink.edu/etdc/view?acc_num=osu1337716744 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Genetics
copy number variation
amylase
type 1 diabetes
genetics
pulsed field gel electrophoresis
segmental duplication
spellingShingle Genetics
copy number variation
amylase
type 1 diabetes
genetics
pulsed field gel electrophoresis
segmental duplication
Rutherford, Andrea Marie
Elucidation of Pattern of Variation for the Amylase Locus in Type 1 Diabetes Patients
author Rutherford, Andrea Marie
author_facet Rutherford, Andrea Marie
author_sort Rutherford, Andrea Marie
title Elucidation of Pattern of Variation for the Amylase Locus in Type 1 Diabetes Patients
title_short Elucidation of Pattern of Variation for the Amylase Locus in Type 1 Diabetes Patients
title_full Elucidation of Pattern of Variation for the Amylase Locus in Type 1 Diabetes Patients
title_fullStr Elucidation of Pattern of Variation for the Amylase Locus in Type 1 Diabetes Patients
title_full_unstemmed Elucidation of Pattern of Variation for the Amylase Locus in Type 1 Diabetes Patients
title_sort elucidation of pattern of variation for the amylase locus in type 1 diabetes patients
publisher The Ohio State University / OhioLINK
publishDate 2012
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1337716744
work_keys_str_mv AT rutherfordandreamarie elucidationofpatternofvariationfortheamylaselocusintype1diabetespatients
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