SPR L17 Genetics Module Overview Flashcards Preview

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Flashcards in SPR L17 Genetics Module Overview Deck (13):

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

  1. Where are the mutations seen?
  2. What is this syndrome?
  3. What are the features of marfan's syndrome?

  1. Mutations in Fibrillin gene

  2. Connective tissue disorder (Lincoln may have been affected)

  3. Joint flexibility/hypermobility

    Crowded teeth

    High arched palate


    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

  1. What is this?
  2. Which enzyme is commonly absent?
  3. How is a diagnosis made?
  4. What is the treatment?

  1. A severe form of Mucopolysaccharidosis I (Hurler disease). Without a bone marrow transplant, death occurs by 8-10 years. 

  2. Absence of lysosomal hydrolase alpha-L- iduronidase (IDUA). Cataract seen in pic

  3. Urine for Glycosaminoglycans (GAG’s), blood for white cell enzymes to biochemistry lab. 

  4. 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 

  1. Other disorders may mimic Down syndrome so if karyotype normal, what should be done next? 


  1. 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.