SPR L17 Genetics Module Overview Flashcards
Chromosomes Vs DNA
Outline the stages from cells to genes
100 trillion cells
nucleus in each cell
each nucleus has 46 chromosomes arranged in 23 pairs
one chromosome from every pair is from each parent
chromosomes are filled with tightly coiled DNA strands
genes are segments of DNA that contain instructions to make proteins (building blocks of life)
What types of genetic disease are there?
Give examples
Chromosome abnormalities e.g. Down syndrome, Edwards syndrome
Single gene disorders
- Autosomal Dominant e.g. Marfan Syndrome, HNPCC
- Autosomal Recessive e.g. Cystic fibrosis, Hurler syndrome
What are the characteristics of AD inheritance?
- Vertical transmission through generations
- Male to male transmission possible
- Males and females equally affected
- Offspring risk is 1 in 2 for an affected parent
- Reduced penetrance and variable expression
Give examples of AD Inheritance conditions
Marfan Syndrome, HNPCC
AD Inheritance - Marfan’s Syndrome
- Where are the mutations seen?
- What is this syndrome?
- What are the features of marfan’s syndrome?
- Mutations in Fibrillin gene
- Connective tissue disorder (Lincoln may have been affected)
- Joint flexibility/hypermobility
Crowded teeth
High arched palate
Scoliosis
Abnormal chest – (pectus excavatum)
Pes planus (flat feet)
Arachnodactyly (long fingers and toes)
Tall stature Rachmaninov may have had the condition
Aortic dissection: Sudden death by aortic rupture can be prevented by cardiac screening (cardiac ECHO, Chest X- Ray, ECG)
Congenital valve abnormalities
What are the characteristics of AR inheritance?
- Usually only members of one sibship affected
- Males and females equally affected
- May be associated with parental consanguinity
- Offspring risk is 1 in 4 for carrier parents
- Risk low for offspring of an affected parent
- Disorders usually present in childhood & are severe
Give examples of Autosomal Recessive conditions
Cystic fibrosis, Hurler syndrome
AR Inheritance - Hurler’s Disease
- What is this?
- Which enzyme is commonly absent?
- How is a diagnosis made?
- What is the treatment?
- A severe form of Mucopolysaccharidosis I (Hurler disease). Without a bone marrow transplant, death occurs by 8-10 years.
- Absence of lysosomal hydrolase alpha-L- iduronidase (IDUA). Cataract seen in pic
- Urine for Glycosaminoglycans (GAG’s), blood for white cell enzymes to biochemistry lab.
- If confirmed, DNA testing for mutations within the Hurler gene IDUA
- Enzyme replacement therapy
- Bone marrow transplant before 2 years
Chromosomal Disorders
Trisomy 21 - Down syndrome
Describe the hand features present
Simian crease
Short 5th finger (clinodactyly)
Broad hands
Short 5th metacarpal
[Normal feature in ~5% population]
Chromosomal Disorders
Trisomy 21 - Down syndrome
What are the different types of Down syndrome?
- Increased maternal age - 95% non- dysjunction
- 3% translocation (esp. 14;21 of which 50% familial)
- 2% mosaic
Karyotype helpful to determine which type of tri21
Chromosomal Disorders
Trisomy 21 - Down syndrome
What are the risks associated with increasing maternal age?
See picture
Other disorders
- Other disorders may mimic Down syndrome so if karyotype normal, what should be done next?
- array cytogenetic analysis (a-CGH) is next test
If dysmorphic child, a-CGH is the investigation of choice, but if Down syndrome is most likely, a karyotype is still the best test as it will show if mosaic or translocation Down syndrome is present.
Learning Objectives
- Be able to describe clinical features of common autosomal dominant Mendelian diseases [e.g. Marfan Syndrome], and autosomal recessive diseases [e.g. Cystic fibrosis and Hurler syndrome].
- Understand cytogenetic abnormalities such as Down syndrome and be able to distinguish the main types of Down syndrome.
