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Finding the underlying genotype behind a familial embolic stroke of unknown origin

Kaur, Damandeep (2019) BINP50 20181
Degree Projects in Bioinformatics
Popular Abstract
Looking for mutations causing stroke in families

For functioning, brain needs uninterrupted supply of blood with oxygen and nutrients. Arteries carry purified blood from heart to brain. If any of the blood vessels in the brain bursts or blocked, brain cells start dying and cause stroke. When stroke has occurred due to blockage in a blood vessel, it is called ischemic stroke. If this blockage is due to a clot formed in the heart or any other part of the body and then travelled to the brain through arteries, it is called embolic stroke. If the blockage is due to a clot developed inside the brain blood vessel, it is called thrombotic. Stroke is second largest cause of death worldwide and the genetic causes along with environmental factors... (More)
Looking for mutations causing stroke in families

For functioning, brain needs uninterrupted supply of blood with oxygen and nutrients. Arteries carry purified blood from heart to brain. If any of the blood vessels in the brain bursts or blocked, brain cells start dying and cause stroke. When stroke has occurred due to blockage in a blood vessel, it is called ischemic stroke. If this blockage is due to a clot formed in the heart or any other part of the body and then travelled to the brain through arteries, it is called embolic stroke. If the blockage is due to a clot developed inside the brain blood vessel, it is called thrombotic. Stroke is second largest cause of death worldwide and the genetic causes along with environmental factors are responsible for its occurrence.

Embolic stroke has been passed through generations in families and individuals at young age start showing early symptoms of stroke. Other genetic factors like high blood pressure, diabetes, high cholesterol and irregular heartbeat increases the risk. Environmental factors like smoking, high alcohol intake, poor diet, inadequate physical activity and obesity also increase the risk of stroke occurrence. Families with stroke have similar kind of lifestyle and are exposed to similar environmental factors, which may also lead to additive cause of the occurrence of stroke.

To know the underlying cause of occurrence of stroke in the family members, one solution could be to look for mutations in their DNA. Mutations are alterations in DNA sequences of the genome of an individual. Two Finnish families in which embolic stroke passed through generations were studied. Human DNA is consists of coding sequences, which is only 1.5% of total DNA and a non-coding part. Coding DNA codes for proteins, which play roles in overall functioning of the body and non-coding codes for nothing but helps in regulation and other processes. 85% of disease related mutations are found in coding region. So in the current study mutations were looked for only in coding region.

Alteration in single nucleotide at a specific position in the DNA are called single nucleotide polymorphism (SNP). SNPs are present in more than 1% of population and single nucleotide variations which are present in less than 1% of population are called single nucleotide variant (SNV). Single nucleotide variations are passed through generations in many rare genetic diseases. In this study, common SNVs were looked for in both families, which may have been the cause of this familial stroke. The mode of inheritance in this type of stroke is autosomal dominant which means that even if the mutation is present in one of the chromosomes, it will result in occurrence of the disease.
After filtering out SNPs, variants were further filtered which follow the autosomal dominant pattern and have high impact on alteration of role in protein. Filtered out variants were compared and 7 deletions in nucleotides were found in both families while 10 common genes with mutations were found but at different positions. Out of these 10 genes, 3 genes have significant role in stroke phenotype. Due to smaller number of individuals in the study, the above results cannot be confirmed. Further work is required for confirmation of the results with bigger sample size. Also, there are some SNPs reported in noncoding region which are responsible for stroke. So if whole genome sequencing data could be used and other environmental factors included in the study, improved results would probably be achieved.


Master’s Degree Project in Bioinformatics 30 credits 2018 Department of Biology, Lund University

Supervisor: Björn Canbäck

Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
author
Kaur, Damandeep
supervisor
organization
course
BINP50 20181
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8979455
date added to LUP
2019-06-04 16:32:13
date last changed
2019-06-04 16:32:13
@misc{8979455,
  author       = {{Kaur, Damandeep}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Finding the underlying genotype behind a familial embolic stroke of unknown origin}},
  year         = {{2019}},
}