What is the lifetime frequency of genetic disorders?
670 per 1000
What are the three broad categories of genetic disorders?
Single gene mutations with large effects; chromosomal disorders; complex multigenic disorders (most common)
Multiple variations of the same gene is referred to as:
Describe Mendelian disorders.
Disorders passed on by mutations that affect single genes and have large effects
What are the major types of point mutation?
Silent, missense, and nonsense
What are the two types of missense mutation?
Conservative (similar amino acid replacement) and nonconservative (very different amino acid replacement)
What kind of effects can deletions within introns have?
Promoters, enhancers, splicing junctions, and other regulatory genes can be altered (often decreasing gene expression)
In what situation are deletions or insertions of DNA not going to result in a frameshift mutation?
If the deletion or insertion is a multiple of three nucleotides
What are some examples of disorders associated with trinucleotide-repeat mutations? Which trinucleotides are involved in each disorder?
Fragile X syndrome (CGG), Huntington's disease (CAG), myotonic dystrophy (CTG), Friedrich's ataxia (GAA)
What disorder types don't fit neatly into the three main types (chromosomal abnormalities, single gene mutations, and multigenic disease)?
Trinucleotide-repeats, mitochondrial inheritance, imprinting, mosaicism
When do sickle cell heterozygotes manifest red blood cell sickling?
Only after unusual circumstances like lowered oxygen tension
A single mutant gene may lead to many end effects. What is this called?
What is it called when mutations at several genetic loci may produce the same trait?
What are some forms by which single-gene mutations are transmitted (3)?
Autosomal dominant, autosomal recessive, and X-linked
Do any patients with autosomal dominant disorders not have affected parents?
Yes, these patients are the result of new mutations (seem to occur in the germ cells of relatively old fathers)
Do autosomal dominant diseases display variation in penetrance and expressivity?
Which protein genes are more likely to be affected in autosomal dominant disorders?
Key structural proteins; metabolic pathway-regulating feedback inhibitors
Which is more common, loss-of-function or gain-of-function mutations?
What genetic disorder category is the largest of the Mendelian disorders?
Autosomal recessive disorders
What percentage of sex-linked disorders are X-linked? How many of these are recessive?
What inheritance pattern does Marfan syndrome show?
What extracellular glycoprotein is deficient in Marfan syndrome?
Lack of fibrillan-1 causes what general effects in Marfan syndrome?
Lack of tropoelastin scaffolding; excessive TGF-beta activation
What are the main abnormalities in Marfan syndrome?
Skeletal abnormalities, subluxation or dislocation of the lens, mitral valve prolapse, and ascending aortic dilation
What is the main course of treatment for Marfan syndrome?
Beta-blockers (reduce heart rate and aortic wall stress)
What group of disorders is characterized by defects in the synthesis or structure of fibrillar collagen?
Ehlers-Danlos Syndromes (VI) (also, osteogenesis imperfect and Alport syndrome)
Which Ehlers-Dalos subtypes are autosomal recessive?
Describe vascular Ehlers-Danlos Syndrome.
Thin skin, arterial or uterine rupture, bruising, small joint hyper extensibility; autosomal dominant
Describe classic Ehlers-Danlos Syndrome.
Skin and joint hypermobility, atrophic scars, easy bruising; autosomal dominant
What is familial hypercholesterolemia?
An autosomal dominant disease in which LDL receptors are under expressed