Mendelian Genetics- Leture 8/26/21 Flashcards
Pedigrees
A method of taking a family history to determine the cause of the disease
Unit inheritance
Genes are inherited as a unit, there is no in between/ parental phenotypes do not blend
Dominant inheritance
- Only one mutated gene copy is necessary for expression
- Multiple generations are affected
- Males and females equally likely
- Male to male transmission observed
- Unaffected individuals have unaffected children
Achondroplasia
- The most common skeletal dysplasia
- Short arms and legs, large head and characteristic facial features
- Intelligence and life span are normal
- autosomal dominant mutation
Variable expressively
Features of a disorder may vary between affected individuals, even in the same family
Marfan syndrome
- Systemic disorder of connective tissue
- High degree of clinical variability including ocular, skeletal and cardiovascular symptoms
- Autosomal dominant
Incomplete penetrance
- Not all individuals with a mutation have phenotypic effects
Ex; BRCA mutation, risk factor for breast and ovarian cancer, though not everyone develops these disorders
New (de novo) mutations
- New gene mutations can occur and are often fount in “hot spots” gametes or early embryo
Recessive inheritance
- Two mutated gene copies are necessary for the expression of trait, need from both parents
- Usually only one generation is affective, parents are often not affective
- Males and females are equally likely to be affected
- Consanguinity may be present
- Ethnic disposition may be noted, penetrance is usually complete
Sickle cell anemia
Autosomal recessive disease that is more common in African American population, characterized by pain and organ damaged due to cell aggregation
Hemophilia
An X-linked recessive inheritance, which is common with consanguinity, English royal family, bleeding disorder factor 9 and 10 which causes internal bleeding
X-linked recessive inheritance
- Males more likely to get infected
- Male to male transmission not observed
- Multiple generations may be infected
- All daughters of affected males are carriers
- “Carrier” females may show mild expression
Lyonization
Random X chromosomes are turned off in every cell in early embryo development for dosage compensation
Skewed X-inactivation
When more of one X chromosome is inactivated in a given tissue, may lead to symptomatic “carriers
Duchenne Muscular Dystrophy
- Progressive disease of the skeletal muscle
- Presents in early childhood, dilated cardiomyopathy
- X-linked recessive
45,X karyotype
Turner syndrome, displays X-linked diseases
Incontinentia Pigmenti
X-linked dominant, disorder of the skin, hair, teeth, nails, eyes, and central nervous system, usually fatal if no regular X-compensation
Mitochondrial DNA
Codes for 2 rRNAs, 22 tRNAs, and about 13 subunits for ox phos. Most Ox phos subunits still come from genomic DNA
MELAS
Mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes, common mitochondrial inhearitance
Heteroplasmy
Mixture of normal and abnormal mtDNA
Homoplasmy
All my DNA is the same (normal or abnormal)
Mitochondrial genetic bottleneck
There is a random distribution of mitochondria and therefore mirochondrial DNA each time a cell divides
Threshold effect
A certain percentage of abnormal mtDNA is tolerated without symptoms, may differ within individuals
Principles of mitochondrial inheritance
The percentage of abnormal mtDNA can change over time, in different tissues due to random genetic drift or a selective advantage
