Genetics Flashcards
3 Primary Types of Mutations
genome mutation
chromosomal mutation
gene variant
genome mutation
loss or gain of an entire chromosome
chromosomal mutation
alteration of a segment of chromosome
gene varient
partial or complete deletion of a gene
how many chromosomes in a typical human
46, 23 pairs
how many autosomal chromosomes pairs
22 pairs
hereditary or familial
condition derived from parents due to a genetic mutation
congenital
condition present at birth; may be hereditary or derived from action or exposure during pregnancy or birth
autosomal dominant
the gene in question is located on one of the 44 numbered, or non-sex, chromosomes
dominant
a single copy of the mutated gene is enough to cause phenotypic expression
clinical manifestations of familial hypercholesterolemia
- Elevated blood cholesterol levels
- Atherosclerosis resulting in cardiovascular disease
- Death before the age of 30 due to uncontrolled CVD
hypercholesterolemia is a mutation of
LDL
receptor mutation that results in impaired uptake of cholesterol into cells
clinical manifestation of marfan syndrome
Skeletal: Long arms, legs, and fingers
Eye: Bilateral dislocation of the lens
Cardiovascular: Aortic root dilation, leading to aortic insufficiency, Myxomatous mitral valve, Ascending thoracic aortic aneurysms, Aortic dissection
T or F osteogenesis imperfecta is heterogeneous
T
osteogenesis imperfecta
Pleiotropic - one gene influences >2 phenotypic traits
80% autosomal dominant
20% autosomal recessive
90% of cases are cause by a mutation of collagene coding gene
pathophysiology of osteogenesis imperfecta
Disease of the Type 1 Collagen: major extracellular protein in the body
Dermis
Connective Tissue of the organs, GI, and vascular system
Bones
osteogenesis imperfecta
Brittle Bone disease
Significant phenotypic heterogeneity between subtypes and within subtypes
X-rays show mild osteopenia
type 1 OI
mildest form of OI
fracture
blue sclera
short stature
75% autosomal dominant inheritance - 25% new mutations
type 2 OI: perinatal lethal
- Most severe form of brittle bone disease
Can be life-threatening presents at or before birth with multiple fractures, bony deformities, significant fragility of nonbony connective tissue, blue sclera, short limbs, small chest, and soft skull
Inadequate and poor quality collagen production
Hallmark characteristic Hips in external rotation & abduction ‘frog-leg’ position
Typically results in death in infancy
Radiologic findings isolated “islands” of mineralization in the skull and beaded appearance in the ribs
Nearly all cases are a new dominant mutation no family history
type 3 OI: severe- progressive deforming
Presents at birth or infancy with progressive bony deformities, multiple fractures, and blue sclera
- Most individuals will require multiple corrective surgeries and lose the ability to walk by early adulthood
Nearly all cases due to dominant mutation – rarely inherited recessively
type 4 OI: moderately severe
- Moderate to severe growth retardation distinguishing factor from Type 1
- Bony deformities, blue sclera, very short ‘long” bones
- Postnatal fractures ranging from severity of Type 1 to Type 3
- Child may fracture later when learning to walk
Severity of symptoms: Type 1 < Type 4< Type 3 < Type 2
cycstic fibrosis clinical
manifestations
- Fibrosis of pancreas
-Recurrent pulmonary infections pneumonia
-Chronic bronchitis, bronchiectasis
-Meconium ileus
-Biliary cirrhosis, leading to impaired absorption of the fat-soluble vitamins A, D, E, and K
-Infertility in males secondary to absence of vas deferens
-Thick and sticky mucus secondary to absence of chloride on cell surface
x linked recessive
Refers to genetic conditions associated with mutations in genes on an X chromosome
x linked recessive: Muscular dystrophy clinical manifestation
- Weakness of pelvis first delayed ability to walk
- Pseudohypertrophy enlargement of calf muscles due to replacement with fat
- Gower maneuver use of hands to rise to a standing position
- Muscle atrophy and weakness progress relentlessly wheelchair dependent by the second decade
- In most cases, death due to respiratory insufficiency and cardiac failure
x linked recessive muscular dystrophy
- profound male predominance; female carriers of the disease are typically asymptomatic
- Clinical course: Disease manifests by the age of 5 years associated muscular weakness leads to immobility by the early teens usually death by the 20s or 30s. Cardiomyopathy and non-progressive cognitive abnormalities are also fairly common
chromosomal inheritance pattern
Mutation of a large segment or entire chromosome
down syndrome
extra copy of chromosome 21 in each cell - trisomy 21
1 in 700 newborns
down syndrome clinical manifestations
Intelectual disability
Characteristic facial features
Hypotonia
Protruding tongue
Congenital heart disease
trisomy 18 clinical manifestation
Heart/organ defects
Small and abnormally shaped head, small jaw and mouth
Clenched fists with overlapping fingers
ehlers-danlos-syndrome
Hereditary collagen disorder characterized by articular hypermobility, dermal hyperelasticity, and widespread tissue fragility
- mutations in at least 20 genes
EDS clinical manifestation
Hyperextensible skin
Fragile tissue
Poor wound healing
Joint hypermobility
Increased propensity for joint subluxation
Muscle weakness
Delayed motor development
Fatigue
Gait defects
Chronic pain
cystic fibrosis mutation
Cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7
cystic fibrosis epidemiology
: 1 in 3500 live births; whites predominantly
duchenne muscular dystrophy epidemiology
1 in 3000 infants; profound male predominance; female carriers of the disease are typically asymptomatic
Clinical course: Disease manifests by the age of 5 years associated muscular weakness leads to immobility by the early teens usually death by the 20s or 30s. Cardiomyopathy and non-progressive cognitive abnormalities are also fairly common
trisomy 18 facts
Individuals with trisomy 18 often have slow growth before birth low birth weight
Due to the presence of several life-threatening medical problems, many individuals with trisomy 18 die before birth or within their first month.
Five to 10 percent of children with this condition live past their first year, and these children often have severe intellectual disability.
Epidemiology: 1 in 5,000 live births
genetic conditions with mixed inheritance patterns
Depending on the condition and the gene involved, the inheritance pattern can be autosomal dominant, autosomal recessive, or X-linked recessive
Ehlers-Danlos Syndrome
PT implications of EDS
Joint stability low resistance, high repetition
Assistive device for loading relief
Bracing to promote joint stability decrease incidence of subluxing
Pain management
