Summary
Summary Locating genes underlying human phenotypes
- Institution
- University Of Leeds (UoL)
Detailed notes on Locating genes underlying human phenotypes
[Show more]
Seller
Follow
Content preview
BLGY1232 Locating genes underlying human phenotypesIf the biochemical basis of the phenotype is known
This usually means we know which enzyme is defective and we know something
about the polypeptide sequence of the enzyme
The protein sequence can be used in a genome database search to identify the
gene sequence in the human genome allowing us to PCR-amplify the dene for
affect and unaffected individuals and identify any mutation in the affected
individuals and their families to see if they are also at risk
Haemoglobin in haemoglobinopathies, Hexosaminidase A in Tay-Sachs disease,
Apolipoprotein E in typeIII hyperlipidaemia, Cystic fibrosis etc.
If we don’t know the biochemical basis of a condition
We have to locate where the gene is in the genome, identify the correct coding
sequence and determine the nature of the mutation and its effect on the protein
encoded
2 statistical approaches can be used; analysis based on genetic linkage or
analysis based on allelic association both rely on genetic variation
(polymorphisms) between individuals
To locate the gene, we need to know where it lies in the genome in relation to
other known sequences that differ between individuals - We need to analyse
how it relates to other polymorphisms and the key point is that the variant
sequence should be maintained within a proportion of the population: it’s not
just a one-off mutation
Polymorphism = The existence of two or more variants (alleles, phenotypes, DNA
sequence variants, chromosome structural variations) at significant frequencies
in the population
Autozygosity mapping
Pedigree analysis in families with a high incidence of consanguineous marriage
Where parents are related, there is a higher frequency of autosomal recessive
inherited disorders
We can try and determine the genotypes of affected individuals and their family
members, to identify the genetic interval within which the disease gene lies; this
, region will be homozygous in affected and heterozygous in unaffected family
members
Genetic polymorphism
The existence of 2 or more variants (alleles, phenotypes, DNA sequence variants,
chromosome structural variations) at significant frequencies in the population
Any genetic variant allele that exists at or above a frequency of 1% of the
population
Any non-pathogenic variation
Polymorphisms can be phenotypic (e.g. different blood groups) – but there are
not very many easily identified phenotypic polymorphisms whose exact genetic
location is known
DNA sequence variations are much more useful, because
(1) There are very many throughout the genome
(2) They can be identified by molecular analysis
(3) They are inherited in a codominant manner and we can identify homo- and
hetero-zygotes
RFLPs - restriction fragment length polymorphisms, usually resulting from
mutations that occurred in RE sites; mutation of a restriction enzyme recognition
site results in loss of a cut site
RFLPs are detectable by Southern blotting This is a laborious process, and so is
not used very often for polymorphism analysis using Southern blotting we can
detect different forms (alleles) of individual genes in individual members of
populations
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller 7joshlyons7. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for £2.99. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
79223 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy revision notes and other study material for 14 years now