Sequencing and DNA Fingerprint Mapping of Overlapping Clones Spanning a 45kb Genomic Region Containing the Human Lysyl Oxidase Gene
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Authors
Thierry, Andrew
Issue Date
1998
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Lysyl oxidase is an extracellular, copper dependent enzyme that initiates the
covalent cross-linking of collagen and elastin. These cross-linkages, which provide
tensile strength and elasticity, are essential to the normal function and structural
integrity of the connective tissue matrix. Increased lysyl oxidase activity has been
reported in fibrotic diseases including hypertension, atherosclerosis, and hepatic and
pulmonary fibrosis, while deficiencies oflysyl oxidase have been observed in cutis
laxis, and X-linked recessively inherited disorders such as Menkes syndrome and
Ehlers-Danlos syndrome subtype IX. Another interesting facet of lysyl oxidase is that
it is identical to the ras-recision gene (rrg) and possesses tumor suppressor activity.
Sequence data exists only for the exons and the first introns, while the
structure of the gene has been well characterized. This project began to uncover the
sequence data 5' and 3' to the gene along with that of the introns to lay the foundation
for further studies of the regulatory sites and controls of the gene. Overlapping
restriction fragments made from previously obtained YAC clones were sequenced
using both primers and nested deletion techniques. A fingerprint digest was also
performed, and together with the sequence data and restriction data, allowed for the
improvement of a previously made map covering the region 5' and 3' to the gene as
well as the 45kb region covering the human lysyl oxidase gene. The information
obtained by this project is currently being used by the lab to sequence the whole
region in hopes that this information will be used in the near future as a form of
genetic therapy for fibrotic diseases and cancers.
Description
v, 31 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.