Mapping Mendelian Disease Flashcards
(34 cards)
What is the Lymphatics system known as?
The Cinderella of the circulatory system
What are the functions of the Lymphatic system?
- Fluid homeostasis
- Immune function
- Fatty acid transport
What is the lymphatics system in regards to the capillary bed?
An integral part of the interweaving network in the capillary bed
What is primary lymphoedema?
- It is a chronic Oedema
- Often progressive
What are the two causes of primary Lymphoedema?
- A developmental abnormality
- A dysfunction of the lymphatics system
How does the phenotypes of primary lymphoedema vary?
- Age of onset
- Site
- Inheritance patterns
- Associated features
- Genetic causes
What are the physical implications of primary lymphoedema?
Lymphoedema can be
- Debilitating
- Embarrassing
- Stressful
- Causes recurrent infections
Why is this research important?
Has no medical cure
How do we study genetic diseases? (PART 1)
Clinically first Through:
- Patients
- Families
How do we study genetic diseases? (PART 2)
It then gets sent to the laboratory for:
- Genetic identification
- Functional studies
How do we study genetic diseases? (PART 3)
It then gets sent back to the clinic for:
- Diagnostic tests
- Counselling
- Treatments
How do we study genetic diseases?
How is gene identification carried out?
Gene identification by gene mapping
- Homozygosity mapping
- Linkage analysis
- GWAS
How do we study genetic diseases?
How do we find disease causing mutations?
Through Sequencing
How do we study genetic diseases?
How do we prove they cause disease?
Using in silico, in vitro and in vivo tools
What is genetic linkage?
Genetic linkage is the tendency for alleles at neighbouring loci to segregate together at meiosis. Therefore to be linked, two loci must lie very close together
What is a haplotype?
- Defines multiple alleles at linked loci
- Mark chromosomal segments which can be tracked through pedigrees and populations
When is crossing over likely to happen?
Most likely to happen During meiosis between loci separated by some distance than those close together
How can we use information about linked alleles to identify disease causing genes?
1). If an allele is linked to a disease locus, the same allele will be inherited by 2 affected relatives than expected by chance
2). If the alleles and the disease locus are linked, all the affected individuals in a family are more likely to inherit this haplotype block
How can we use information about linked alleles to identify disease causing genes?
3). If the alleles and the disease locus are unlinked to the disease locus, the affected individuals in a family are less likely to inherit the same marker alleles.
How is linkage analysis used?
- Gene mapping tools
- Using observed loci (alleles) to draw interferences about an unobserved locus (disease gene)
- Family based design
- The goal is to find genomic regions linked to the disease
What two processes that identifies the cause of primary lymphoedema?
Traditional linkage analysis and Sanger sequencing identifies the cause of autosomal recessive form of primary lymphoedema
What is generalised lymphatic dysplasia? Hennekam syndrome (HS)
- Antenatal hydrops with ascites and pleural effusions
- Oedematous at birth
- Intestinal lymphangiectasia
- Peripheral lymphoedema; arms, legs, face
- Mild developmental delay
Steps for something idk
1). First take a pedigree and get as many DNA samples as possible
2). Use some kind of tool to observe alleles (generating genotyping data for your pedigree)
Steps for something idk (PART 2)
3). Generate a file with your pedigree information plus the genotyping data from the SNP array
4). Run your file in a linkage programme
