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Flashcards in Pathobiology Deck (162)
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1

What is alkaptonuria?

Homogentistic acid accumulates in joints, causing artiste damage and back pain
- Kidney stones
- Blackening of urine
Inherited as autosomal recessive
Inborn errors of metabolism

2

Name some autosomal recessive inherited diseases?

Alkaptonuria
Cystic fibrosis

3

Name some autosomal dominant inherited diseases

Brachydactyly
Huntington's disease

4

Name some autosomal co-domiant inherited diseases

Sickle cell anaemia

5

Name some x linked inherited diseases

Duchenne muscular dystrophy
X linked mental retardation
Haemophilia

6

What are the symptoms and cause of sickle cell anaemia?

- Painful
- Life threatening
- Erythrocytes sickle shaped - can't carry as much oxygen
- Caused by a single point mutation in the codon for amino acid 6 in B- global subunit
- Causes haemoglobin tetrameters containing HBs to form large insoluble polymers which distort erythrocytes shape

7

Where and why is the frequency of the sickle cell anaemia allele (HBs) high?

High in sub saharan countries
- Prevalence 2%
- Allele carrier is 10-40%
Heterozygous provides resistance to malaria

8

What has karyotyping allowed to happen?

Allows each chromosome to be distinguished
- Abnormalities in banding due to mutagens rearrangements can be associated with specific phenotypes
- Genes can be tapped to specific chromosomal locations

9

What is Aniridia?

An autosomal dominant phenotype caused by deletion or loss of function point mutations in one copy of the gene

10

What is Duchenne Muscular Dystrophy (DMD)?

Progressive muscle damage and wasting disease
Lethal in childhood or early adulthood

11

What gene is responsible for Duchenne Muscular Dystrophy?

- Was identified by DNA sequencing
- DNA sequence deleted form the X chromosome of DMD patients
- It is the dystrophin gene that is affected which is the largest known human gene
- Dystrophin protein is responsible of connecting each muscle fibre to the extracellular matrix - integrity

12

What is Huntington's disease?

A progressive, late-onset, inherited neurodegenerative disorder
- Dementia and movement disorder

13

What is the pathology of Huntington's disease?

The brain of a Huntington's disease patient has suffered massive neuronal loss in the basal ganglia and has dilated lateral ventricles
- Caused by an expansion of the repeated CAG sequence in the Huntingtin gene
- This expansion makes the protein toxic to neurones

14

Name an animal virus genome the contains genes that can cause cancer ?

Rous Sarcoma Virus
- contains the v-src oncogene
- Encodes for an abnormally hyperactive version of tyrosine kinase
- Dominant gain of function

15

Name an example of a cancer that can be caused by a loss of function mutation

Retinoblastoma
- can be hereditary or non hereditary
- Can be bilateral or unilateral
- Caused by loss of function of a tumour suppressor gene (both alleles) - more likely to happen if inherited one mutated allele

16

How can chromosomal rearrangements lead to cancer?

- Disruption, eructation or the reassembling of chromosomes

17

How can Single Nucleotide Polymorphisms (SNP's) be used to identify DNA sequence associated with common diseases?

- There are a total of 3x10^7 SNPs in the human genome
- Provide detailed map of DNA sequence variation across the genome
- Can compare SNP's in a group of patients with a specific disease to the SNP's of healthy people
- Any common differences can be associated with that disease
- These studies are called genome wide association studies (GWAS)

18

What is imprinting of genes in animals?

When particular regions of chromosomes have structural modifications to stop transcription e.g. methylation of DNA sequences
- The structural modification are introduced to chromosomes of the sperm and eggs and remain in somatic cells of the offspring but are removed during germ cell production

19

How is methylation an example of the imprinting of genes?

- Methylation of DNA on cytosine bases is a hallmark of imprinted chromatin
- Switches genes off by recruiting repressors and binding proteins

20

What is a paternal and maternal imprint?

Maternal
- When maternal gene has a structural modification so is not expressed
- Paternal gene is expressed
- Gene carries a maternal imprint
- During oogenesis
Paternal
- When paternal gene has a structural modification so is not expressed
- Maternal gene is expressed
- Gene carries a paternal imprint
- During spermatogenesis

21

Explain UBE3A and SNORD116 as an example of gene imprinting

Maternal imprint on SNORD116
Paternal imprint on UBE3A
An example of reciprocal imprinting
Only SNORD116 expressed form paternal and UBE3A from maternal
- Maintained in somatic tissue
- Removed in germ cell development and reestablished

22

What disease occurs when maternal copy of SNORD116 is imprinted and paternal copy mutated?

No functional copy of SNORD116
Prader-willi syndrome
- Low muscle tone
- Cognitive disability
- Morbid obesity

23

What disease occurs when paternal copy of UBE3A is imprinted and maternal copy mutated?

No functional copy of UBE3A
Angelman syndrome
- Cognitive disability
- Sleep disturbance
- Seizures
- Frequent smiling

24

What is epidemiology?

Basics science concerned with the patterns of disease frequency in human population

25

What extrinsic and intrinsic factors can cause disease?

Extrinsic
- Physical
- Socioeconomic
Intrinsic
- Age
- Sex
- Behaviour
- Immunisation

26

Give an example of a migrant study that shows environmental factors causing disease?

Prevalence of certain cancers e.g. stomach and lung are substantially higher in Japan than America
- Decreases if the people from japan migrate to America
- Decreases further in the offspring of the immigrants
=> suggests environmental over genetic factors

27

How is cholera shown to show environmental causes of disease?

- There was poor access to safe water
- Caused by vibrio cholera
- prevalence 50% in unprepared communities but only 1% well organised
- Kills 6 million a year

28

What is the mortality associated with smoking?

320+ UK deaths every day from smoking
1/5 all deaths across all ages
7.5 years average loss of life expectancy

29

What are the major health consequences of smoking?

- Cancer (lung, mouth, bladder, pancreas)
- Respiratory disease (COPD)
- Vascular disease (Coronary heart disease, stroke, peripheral vascular disease)
- Pregnancy and birth complications (premature birth)
- Pulmonary emphysema

30

What is pulmonary emphysema?

- Breakdown of extracellular matrix in lungs
- Alveoli burst
- Macrophages secrete chemotactic factors and secrete proteases which digest lungs
- Oxidants and free radicals in smoke release antitrypsin making proteases more active
- Increased risk of infection