Finding the gene for hereditary motor and sensory neuropathy with pyramidal signs - PowerPoint PPT Presentation

1 / 32
About This Presentation
Title:

Finding the gene for hereditary motor and sensory neuropathy with pyramidal signs

Description:

too many HSP genes and they can be very large. Solution: ... baclofen (Lioresal) Cramps. heat massage magnesium. quinidine. For bladder urgency ... – PowerPoint PPT presentation

Number of Views:45
Avg rating:3.0/5.0
Slides: 33
Provided by: anzacresea
Category:

less

Transcript and Presenter's Notes

Title: Finding the gene for hereditary motor and sensory neuropathy with pyramidal signs


1
Classification of hereditary spastic paraplegias
2
(No Transcript)
3
(No Transcript)
4
(No Transcript)
5
(No Transcript)
6
(No Transcript)
7
(No Transcript)
8
normals
affecteds
9
(No Transcript)
10
Gene sequencing
11

mutation GTAgtGGA val 148gly
12
Problem- too many HSP genes and they can be very
large.
Solution collaborators specialising in
different genes new methods rapid
screening chips with many mutations
13
MANAGEMENT
- Symptomatic and presymptomatic counselling -
Support of physical and social environment - Maint
ain independence - Reproductive issues -
counselling - antenatal testing and
alternatives.
14
Drug treatments
  • Spasticity
  • antispasmodics
  • baclofen (Lioresal)
  • Cramps
  • heat massage magnesium
  • quinidine
  • For bladder urgency
  • oxybutynin (Ditropan)

15
(No Transcript)
16
Genetic Counselling issues
  • Determine need
  • Check diagnosis
  • Check family history
  • Mode of inheritance or (availability of direct
    test)
  • - DNA - Protein
  • - Cytogenetic - Ultrasound
  • Make test/prediction (write it down for family)

17
DIFFICULT ISSUES
- Family disruption - Denial of access (i)
to at risk individuals (ii) to affected
individual for testing - Childrens rights -
Societys rights
18
SPECIFIC TREATMENTS
  • - Replace product. (e.g. factor VIII)
  • - Block product
  • - Pharmacological treatment.
  • Gene therapy
  • ?? Stem cell therapy

19
(No Transcript)
20
Aim To identify the defective gene causing HSP
HMN with pyramidal signs
  • To map the CMT with pyramidal signs gene mutation
    to a chromosomal locus
  • To fine map the critical region
  • To locate and screen genes for mutations in
    linked CMT with pyramidal signs families.

21
Mapping a defective gene on the chromosome
  • Family selection and clinical examination
  • Exclusion of known HSP loci in the selected
    families
  • Genome screen and linkage analysis.

22
Family selection and clinical examination
  • Family selection is based on the clinical
    features, neurophysiology, pathology and mode of
    inheritance
  • We have 30 families available for this study
  • Two large families were selected for genetic
    study.

23
Family
24
Family 105
25
Exclusion of known HSP/HMN loci in the selected
families
26
linkage analysis
  • Linkage analysis is a statistical technique to
    test the co-segregationof trait and marker. If a
    particular form of a marker, called an allele, is
    always associated with a high value of the trait
    then this particular marker is located close to a
    gene influencing this trait.
  • To perform a linkage analysis
  • Identifying families which segregate a disease
    trait
  • Multigeneration families segregating a particular
    trait with multiple affected individuals.
  • Genotyping family with genetic markers
  • the human genome project has produced genetic
    maps containing markers that are spaced at 1 cM
    intervals on average.
  • Performing linkage analysis to identify
    chromosomal location of disease.

27
Testing power to detect linkage
 

 
28
Genome Screen
  • A 5 cM genome screen was performed at Australian
    Genome Research Facility (AGRF)
  • A total of 28 individuals were genotyped (12
    individuals definitely affected)
  • Genome screen took 2 months to obtain genotype
    data for analysis.

29
Maximum 2-point LOD score generated from genome
screen for each chromosome
Maximum 2-point LOD score
Chromosome
30
  • L O D T A B L E R E P O R T
  •  
  • Order 0.0 0.01 0.05 0.1 0.2
    0.3 0.4
  • ----- ------- ------- ------- ------- -------
    ------- -------
  • D1S468 -6.34 -1.42 -0.25 0.07 0.16
    0.08 0.01
  • D1S2660 2.76 2.73 2.61 2.41 1.89
    1.27 0.61
  • D1S214 -0.90 2.33 2.71 2.61 2.07
    1.36 0.62
  • D1S450 -2.39 -1.48 -0.09 0.47 0.80
    0.70 0.37
  • D1S2667 -3.17 -1.09 -0.44 -0.21 -0.07
    -0.05 -0.04
  • D1S434 0.49 0.50 0.53 0.52 0.42
    0.27 0.12
  • D1S507 -2.13 0.34 0.99 1.19 1.16
    0.88 0.47
  • D1S2697 -3.27 -1.04 -0.21 0.15 0.37
    0.33 0.17
  • D1S2644 -4.40 -1.77 -0.83 -0.35 0.06
    0.16 0.11
  • D1S199 -3.52 -0.48 0.26 0.53 0.62
    0.48 0.25
  • D1S2684 -1.90 0.00 0.62 0.79 0.74
    0.53 0.27
  • D1S234 -3.95 -1.56 -0.73 -0.33 0.01
    0.11 0.09
  • D1S233 -0.13 -0.06 0.12 0.24 0.28
    0.21 0.09

31
I
II
III
IV
V
32
(No Transcript)
Write a Comment
User Comments (0)
About PowerShow.com