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Flashcards in Pathobiology Deck (162)
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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


Name some autosomal recessive inherited diseases?

Cystic fibrosis


Name some autosomal dominant inherited diseases

Huntington's disease


Name some autosomal co-domiant inherited diseases

Sickle cell anaemia


Name some x linked inherited diseases

Duchenne muscular dystrophy
X linked mental retardation


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


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


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


What is Aniridia?

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


What is Duchenne Muscular Dystrophy (DMD)?

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


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


What is Huntington's disease?

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


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


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


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

- 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


How can chromosomal rearrangements lead to cancer?

- Disruption, eructation or the reassembling of chromosomes


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)


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


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


What is a paternal and maternal imprint?

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


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


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


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


What is epidemiology?

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


What extrinsic and intrinsic factors can cause disease?

- Physical
- Socioeconomic
- Age
- Sex
- Behaviour
- Immunisation


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


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


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


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


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