The Sequence and Function Relationship of Elastin: How Repetitive Sequences can Influence the Physical Properties of Elastin
Elastin is an essential extracellular protein that is a key component of elastic fibres, providing elasticity to cardiac, dermal, and arterial tissues. During the development of the human cardiovascular system, elastin self-assembles before being integrated into fibres, undergoing no significant tur...
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ndltd-LACETR-oai-collectionscanada.gc.ca-OTU.1807-317802013-04-17T04:19:17ZThe Sequence and Function Relationship of Elastin: How Repetitive Sequences can Influence the Physical Properties of ElastinHe, DavidElastinBioinformaticsLow complexity sequenceBiomaterial0715Elastin is an essential extracellular protein that is a key component of elastic fibres, providing elasticity to cardiac, dermal, and arterial tissues. During the development of the human cardiovascular system, elastin self-assembles before being integrated into fibres, undergoing no significant turnover during the human lifetime. Abnormalities in elastin can adversely affect its self-assembly, and may lead to malformed elastic fibres. Due to the longevity required of these fibres, even minor abnormalities may have a large cumulative effect over the course of a lifetime, leading to late-onset vascular diseases. This thesis project has identified important, over-represented repetitive elements in elastin which are believed to be important for the self-assembly and elastomeric properties of elastin. Initial studies of single nucleotide polymorphisms (SNPs) from the HapMap project and dbSNP resulted in a set of genetic variation sites in the elastin gene. Based on these studies, glycine to serine and lysine to arginine substitutions were introduced in elastin-like polypeptides. The self-assembly properties of the resulting elastin-like polypeptides were observed under microscope and measured using absorbance at 440nm. Assembled polypeptides were also cross-linked to form thin membranes whose mechanical and physical properties were measured and compared. These mutations resulted in markedly different behavior than wild-type elastin-like proteins, suggesting that mutations in the repetitive elements of the elastin sequence can lead to adverse changes in the physical and functional properties of the resulting protein. Using next-generation sequencing, patients with thoracic aortic aneurysms are being genotyped to discover polymorphisms which may adversely affect the self-assembly properties of elastin, providing a link between genetic variation in elastin and cardiovascular disease.Parkinson, John2011-112012-01-09T20:44:37ZNO_RESTRICTION2012-01-09T20:44:37Z2012-01-09Thesishttp://hdl.handle.net/1807/31780en_ca |
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Elastin Bioinformatics Low complexity sequence Biomaterial 0715 |
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Elastin Bioinformatics Low complexity sequence Biomaterial 0715 He, David The Sequence and Function Relationship of Elastin: How Repetitive Sequences can Influence the Physical Properties of Elastin |
description |
Elastin is an essential extracellular protein that is a key component of elastic fibres, providing elasticity to cardiac, dermal, and arterial tissues. During the development of the human cardiovascular system, elastin self-assembles before being integrated into fibres, undergoing no significant turnover during the human lifetime. Abnormalities in elastin can adversely affect its self-assembly, and may lead to malformed elastic fibres. Due to the longevity required of these fibres, even minor abnormalities may have a large cumulative effect over the course of a lifetime, leading to late-onset vascular diseases. This thesis project has identified important, over-represented repetitive elements in elastin which are believed to be important for the self-assembly and elastomeric properties of elastin. Initial studies of single nucleotide polymorphisms (SNPs) from the HapMap project and dbSNP resulted in a set of genetic variation sites in the elastin gene. Based on these studies, glycine to serine and lysine to arginine substitutions were introduced in elastin-like polypeptides. The self-assembly properties of the resulting elastin-like polypeptides were observed under microscope and measured using absorbance at 440nm. Assembled polypeptides were also cross-linked to form thin membranes whose mechanical and physical properties were measured and compared. These mutations resulted in markedly different behavior than wild-type elastin-like proteins, suggesting that mutations in the repetitive elements of the elastin sequence can lead to adverse changes in the physical and functional properties of the resulting protein. Using next-generation sequencing, patients with thoracic aortic aneurysms are being genotyped to discover polymorphisms which may adversely affect the self-assembly properties of elastin, providing a link between genetic variation in elastin and cardiovascular disease. |
author2 |
Parkinson, John |
author_facet |
Parkinson, John He, David |
author |
He, David |
author_sort |
He, David |
title |
The Sequence and Function Relationship of Elastin: How Repetitive Sequences can Influence the Physical Properties of Elastin |
title_short |
The Sequence and Function Relationship of Elastin: How Repetitive Sequences can Influence the Physical Properties of Elastin |
title_full |
The Sequence and Function Relationship of Elastin: How Repetitive Sequences can Influence the Physical Properties of Elastin |
title_fullStr |
The Sequence and Function Relationship of Elastin: How Repetitive Sequences can Influence the Physical Properties of Elastin |
title_full_unstemmed |
The Sequence and Function Relationship of Elastin: How Repetitive Sequences can Influence the Physical Properties of Elastin |
title_sort |
sequence and function relationship of elastin: how repetitive sequences can influence the physical properties of elastin |
publishDate |
2011 |
url |
http://hdl.handle.net/1807/31780 |
work_keys_str_mv |
AT hedavid thesequenceandfunctionrelationshipofelastinhowrepetitivesequencescaninfluencethephysicalpropertiesofelastin AT hedavid sequenceandfunctionrelationshipofelastinhowrepetitivesequencescaninfluencethephysicalpropertiesofelastin |
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1716580607995150336 |