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Flashcards in Genetics Deck (46):
1

Codominance
Definition
Example

Bole alleles contribute to the phenotype of the heterozygote
Blood Group A, B, AB

2

Variable Expressivity
Definition
Example

Phenotype varies among individual with same genotype
Neurofibromatosis type 1

3

Incomplete Penetrance
Definition
Example

Not all individuals with the mutant genotype show the mutant phenotype
BRCA1 gene mutation do not always result in breast or ovarian cancer

4

Pleiotropy
Definition
Example

One gene contributes to multiple phenotypic effects
PKU

5

Imprinting
Definition
Physiology
Example

Differences in gene expression depend on whether the mutation is of maternal or paternal origin
At some loci, only 2 allele is active depending on which parent it came from
Prader Willi and Angelman's Syndrome

6

Anticipation
Definition
Example

Increased severity or earlier onset of disease in succeeding generations
Huntington's Disease

7

Loss of Heterozygosity
Definition
Example

Two Hits needed for disease, born with one mutation
Retinoblastoma and other tumor suppressors

8

Dominant Negative
Definition
Example

Heterozygote produces disease
Nonfunctional TFs binding prevents wild-type from binding

9

Linkage Disequilibrium
Definition
Where is it measured

Tendency for certain alleles at 2 linked loci to occur together more often than expected by chance
Measured in a population, not in a family, and often varies in different populations

10

Mosaicism
Definition
Where can it occur
Example

Cells in the body differ in genetic make up due to post fertilization loss or change of genetic information during mitosis
Can be germ-line which produces disease not carried by either parent's somatic cells
Bone marrow stem cells --> hematologic mosaic. Fused zygote

11

Locus Heterogeneity
Definition
Example

Mutations at different loci can produce the same phenotype
Marfan's, MEN2B, and Homocystinuria can all cause marfanoid habitus. Albinism

12

Heteroplasmy
Examples

Presence of both normal and mutated mtDNA resulting in variable expression in mitochondrial inherited disease
Myclonic Epilepsy

13

Uniparental disomy
What is it?
How do you tell when the error happened?

Offspring receives 2 copies of a chromosome from 1 parent and no copies from the other
Heterodisomy (heterozygous): Meiosis I error
Isodisomy (homozygous): Meiosis II error or post zygotic loss of 1 chromosome and duplication of the other

14

Hardy-Weinberg Population Genetics
Equation
Assumptions
In X linked recessive disease

(p^2) + 2pq + (q^2) = 1 and p+q=1
No mutations, Selection, Migrations and random mating
The frequency of an X linked recessive disease in males is q and in females is (q^2)

15

Prader-Willi Syndrome
Chromosome
Which allele is not expressed?
What can cause it?
Presentation

Inactivation or deletion on chromosome 15
Paternal allele is not expressed
Can also occur as a result of uniparental disomy
Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia

16

Angelman's Syndrome
Chromosome
Which allele is not expressed?
What can cause it?
Presentation

Inactivation or deletion on chromosome 15
Maternal allele is not expressed
Can also occur as a result of uniparental disomy
Mental retardation, Seizures, Ataxia, Inappropriate laughter

17

Hypophosphatemic rickets
PathoPhys
Presentation
Genetics

↑ Phosphate wasting in PT of kidney
Rickets-like presentation
X linked Dominant

18

Mitochondrial myopathies
Genetics
PathoPhys
Presentation
Histo

Mitochondrial Inheritance
Mutations affecting Mito function
Myopathy and CNS disease (seizures)
Muscle biopsy shows ragged red fibers

19

Familial Hypercholesterolemia
AKA
PathoPhys
Blood test
Heterozygotes vs Homozygotes
Presentation
Risk of what?

Hyperlipidemia Type IIA
Absent of defective LDL receptor
Elevated LDL in blood
Heterozygotes have cholesterol of 300
Homozygotes have cholesterol of 700
Severe atherosclerotic disease in early life. Tendon xanthoma (classically in the achilles tendon)
MI may develop before age 20

20

Hereditary Hemorrhagic Telangiectasia
AKA
What organ system affected? How?
Genetics
Presentation

Osler-Weber-Rendu Syndrome
Disorder of blood vessels with arteriovenous malformations
Autosomal dominant
Telangiectasia, Recurrent Epistaxis, Skin discoloration

21

Hereditary Spherocytosis
Inheritance
What happens?
Mutation
Presentation
Treatment

Autosomal dominant
Spheroid erythrocytes
Spectrin or Ankyrin defective
Hemolytic anemia, ↑ mean corpuscular hemoglobin concentration (MCHC)
Splenectomy is curative

22

Huntington's Disease
Inheritance
Presentation
Gross
PathoPhys
Age of onset
Genetics with chromosome and pathology

Autosomal dominant
Depression, Dementia, Choreiform movements
Caudate atrophy
↓ GABA and ACh in brain
20-50
Huntington gene on chromosome 4 with trinucleotide repeats (CAG) "Hunting 4 food"

23

Marfan Syndrome
Inheritance
Mutation
Organs affected
Presentation
Risks associated with it?

Autosomal dominant
Fibrillin 1 gene mutation
Connective tissue of skeleton, heart, and eyes
Tall w/ long extremities, Hypermobile joints, long tapering fingers and toes (arachnodactyly)
Cystic Medial necrosis of the aorta --> aortic incompetence and dissecting aneurysm, Floppy Mitral Valve, Subluxation of the lenses

24

Neurofibromatosis Type 1
Name
Inheritance
Findings
Chromosome

Von Recklinghausen's Disease
Autosomal dominant
Cafe-au-lait spots, Neural tumors, Lisch nodules (pigmented iris hamartomas)
Long arm of chromosome 17

25

Neurofibromatosis Type 2
Inheritance
Presentation
Genetics with chromosome

Autosomal dominant
Bilateral acoustic schwannomas and Juvenile cataracts
NF2 gene on chromosome 22
"Type 2 = 22"

26

von Hippel-Lindau disease
Inheritance
Findings
What are they at risk for?
Genetics with chromosome
PathoPhys

Autosomal dominant
Hemangioblastomas of retina/cerebellum/medulla
Multiple bilateral renal cell carcinoma and other tumors
Deletion of VHL gene (tumor suppressor) on chromosome 3p
Constitutive expression of HIF transcription factor and activation of angiogenic growth factor

27

Cystic Fibrosis
Inheritance
Genetics with chromosome
PathoPhys with presentation
What happens to the protein

Autosomal recessive
Defect in CFTR gene on chromosome 7
Defective Cl channel --> secretion of abnormally thick mucus that plugs lungs, pancreas, and liver --> recurrent pulmonary infections (Pseudomonas and S aureus), chronic bronchitis, Bronchiectasis, Pancreatic insufficiency (malabsorption and steatorrhea leading to VitKADE deficiency), Nasal polyps, Meconium ileus
Abnormal folding --> degradation before reaching cell surface

28

Normal function of CFTR

secretes Cl in lungs and GI tract and reabsorbs sweat

29

Cystic Fibrosis
Male presentation
Infant presentation
Race affected
Diagnostic test
Treatment

Infertility in males due to bilateral absence of vas deferens
Failure to thrive in infants
Most common lethal genetic disease of whites
↑ concentration of Cl in sweat test
N-acetylcysteine to loosen mucous plugs (cleaves disulfide bonds within mucous glycoproteins)

30

X Linked Recessive Disorders
Names
Presentation in females

"Be Wise, Fool's GOLD, Heeds Silly HOpe"
Bruton's agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry's disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne's (and Becker's) muscular dystrophy, Hunter's Syndrome, Hemophilia A and B, Ornithine transcarbamoylase deficiency
Female carriers may be affected and may have less severe symptoms due to random X chromosome inactivation

31

Duchenne's Muscular Dystrophy
Inheritance
Mutation
PathoPhys
Presentation
Time of onset
Risk of what?
Diagnosis

X linked recessive
Frameshift mutation of dystrophin gene
Accelerated muscle breakdown
Weakness begins in pelvic girdle muscles and progresses superiorly. Pseudohypertrophy of calf muscle. Use of Gower's Maneuver requiring assistance of upper extremities to stand up
Onset before 5 years of age
Risk of Cardiac Myopathy
↑ CPK and muscle biopsy

32

Becker's Muscular Dystrophy
Inheritance
Mutation
Severity
Onset
Diagnosis

X linked mutated dystrophin gene
Less severe
Adolescence or early adulthood
↑ CPK and muscle biopsy

33

Fragile X syndrome
Inheritance
Mutation
PathoPhys
Frequency
Findings

X linked
Trinucleotide repeat disorder (CGG)
Defect affecting methylation and expression of FMR1 gene
2nd most common cause of mental retardation after Down syndrome
Macroorchidism (enlarged testes), Long face with Large jaw, Large everted ears, Autism, MVP

34

Longest human gene

Dystrophin gene
High rate of spontaneous mutation

35

Function of Dystrophin

Helps anchor muscle fibers, primarily in skeletal and cardiac muscle

36

Trinucleotide Repeat Expansion Diseases
Names
Repeat sequence
How does it change over generations

"Try Hunting for My Fried Eggs"
"X-Girlfriend's First Aid Helped Ace My Test"
Fragile X: CGG
Friedreich's ataxia: GAA
Huntington's: CAG
Mytonic dystrophy: CTG
Shows anticipation

37

Down Syndrome
AKA
Frequency
Findings
What are they at risk for?

Trisomy 21 ("Drinking Age is 21")
Most common viable chromosomal disorder and most common cause of genetic mental retardation
Mental retardation, Flat Facies, Prominent Epicanthal Folds, Simian Crease, Gap between 1st 2 toes
Risk for Duodenal atresia, Congenital Heart Disease (ostium primum type ASD), ALL, and Alzheimer's disease

38

Down Syndrome
Cause of trisomy?
Who is at risk?
Diagnosis

95% due to meiotic nondisjunction of homologous chromosomes (advanced maternal age)
4% due to Robertsonian translocation
1% due to Down Mosaicism (no maternal association)
↓ α fetoprotein, ↓ estriol, ↑ β-hCG, ↑ inhibin A, and US shows ↑ Nuchal in 1st trimester translucency

39

Edward's Syndrome
AKA
Findings
What are they at risk for?
Course
Diagnosis

Trisomy 18 ("Election age is 18")
Mental retardation, Rocker-Bottom Feet, Micrognathia (small jaw), Low-Set Ears, Clenched hands, Prominent Occiput
Risk of Congenital Heart Defects
Death within 1 year
↓ α fetoprotein, ↓ estriol, ↓ β-hCG, Normal inhibin A

40

Patau's Syndrome
AKA
Presentation
What are they at risk for?
Course
Diagnosis

Trisomy 13 ("Puberty 13")
Mental retardation, Rocker-bottom feet, Microphthalmia (small eyes), Microcephaly, Cleft lip, Clefp Palate, Holoprosencephaly (forebrain lacks 2 hemispheres), Polydactyly
Risk of Congenital Heart Disease
Death within 1 year
↓ PAPP-A, ↑ free β-hCG, ↑ nuchal translucency

41

Non disjunction in meiosis I

2 homologous chromosomes in 2 cells, Missing chromosome in 2 cells

42

Non disjunction in meiosis II

2 identical chromosomes in 1 cell, 2 normal cells, 1 cell missing a chromosome

43

Robertsonian Translocation
Mechanism
Chromosomes involved

Nonreciprocal translocation. Fusion of 2 acrocentric chromosomes and loss of short arms
13, 14, 15, 21, 22

44

Cri-du-chat Syndrome
What is it?
Presentation
Risk of what?

Congenital microdeletion of short arm of chromosome 5
Microcephaly, Mental Retardation, High pitched crying (mewing), Epicanthal folds
Cardiac Abnormalities (VSD)

45

William's Syndrome
What is it?
Presentation

Congenital microdeletion of long arm of chromosome 7 (including elastin gene)
Elfin facies, Intellectual disability, HyperCa (↑ sensitivity to VitD), well developed verbal skills, extreme friendliness with strangers, Cardiovascular problems

46

22q11 Deletion Syndrome
Presentation
Subtypes
What is it due to?

"CATCH 22"
Variable presentation: Cleft palate, Abnormal facies, Thymic aplasia (leads to T cell deficiency), Cardiac defects, HypoCa secondary to parathyroid aplasia
DiGeorge Syndrome: Thymic, Parathyroid, and Cardiac defects
Velocardiofacial Syndrome: Palate, Facial and Cardiac defects
Aberrant development of 3rd and 4th branchial pouches