lecture 5 Flashcards
single gene disorder
disorders which occur due to alteration in one or both copies of a single gene
autosomal gene
located on one of the 22 pairs of autosomes (non -sex chromosomes)
autosomal dominant disease
an alteration in a single copy of an autosomal dominant gene has a recognizable clinical outcome
what does the transmisson of a disease from male to male (father to son) show
shows us that the condition must be autosomal, non sex chromosomes
penetrance
the percentage of gene carriers who carry a specific genetic variant and actually show clinical symptoms of that disorder.
expression
how the genetic disorder is manifested (what symptoms and clinical features are observed)
what is important to note about people who have an autosomal dominant disorder
they also have family members who are at risk of inheriting the disease
familial hypercholesterolemia symptoms
- higher levels of cholesterol means that plaque builds up in the arteries which can lead to coronary artery disease
- little lumps of fatty tissue
how common is familial hypercholesterolemia
1 in 500
cholesterol
ingested in the diet
synthesized and secreted from the liver
how is cholesterol removed from circulation
via LDL (low density lipoprotein) complex
LDL particles in the bloodstream carry cholesterol.
LDL particles bind to LDL receptors
stages of LDL receptor synthesis in the hepatocyte
- abnormality of LDL receptor synthesis
- abnormality of transport to golgi apparatus
- abnormality of LDL binding by receptor
- abnormality of receptor clustering in coated pit
Type 1 Neurofibromatosis
- multiple benign skin tumors and multiple brown skin patches
- full penetrant but variable expression
Marfan syndrome
- tall stature, long limbs, loose joints, dislocated lense
- fully penetrant with variable expression
Huntington Disease
- manifests with abnormal limb movements, mood changes, progressive dementia
- incurable
- children of person with HD have 50% chance of having abnormal HD gene
Familail Adenomatous Polyposis
- fully penetrant
- develop benign colonic polyps (growths that develop on the inner lining of the colon or rectum)
- untreated will progress to colon cancer
Achondroplasia
- short limbed short stature, and macrocephaly (large head)
- fully penetrant and has a consistent expression.
- high new mutation rate, most people being born to normal stature parents
inheritance of achondroplasia
although a person with achondroplasia is often born to unaffected parents, when that person becomes an adult there is a 50:50 chance of each of their children being similarly affected if there partner is unaffected
results when both parents are affected by a autosomal dominant disorder
- 1 in 4 chance of child being unaffected
- 2 in 4 chance of child with the same condition their parent has
- 1 in 4 chance of being homozygous, more severely affected
haploinsufficiency
genetic condition in which a single functional copy of a gene is not sufficient to maintain normal function
homodimer
gene product interacts with itself
heterodimer
gene product interacts with products of other genes
dominant negative pathogenic variants
genetic mutations that result in the production of a mutant protein that interferes with the production of the normal protein
dominant negative pathogenic variant - Marfan syndrome
fibrillin 1 protein monomers polymerise together to make microfibrils
partly functional pathogenic variant will produce unstable protein
Dominant negative pathogenic variant - Osteogenesis Imperfecta
Type 1 collagen genes produce collagen proteins which are expressed in bone
missense pathogenic variants in Col1A1 destablise triple protein helix causing Oesteogenesis Imperfecta
Charcor Marie Tooth disease
- slowly progressive weakness and loss of feeling in lower legs
- high arches
absent reflexes
