Principles of Genetic Inheritance

Question 1

How do you analyze a pedigree?

Answer 1

Read the proband. It will give you the generation (II,II,III,…) and then a number. Count from the left to this number.

Question 2

How many alleles are required for expression if it is autosomal dominant?

Answer 2

Only 1 allele (Aa would show).

Question 3

In what generations is the trait expected in autosomal inheritance?

Answer 3

In every generation. Recurrent risk is 50%.

Question 4

How many alleles are required for expression in autosomal recessive?

Answer 4

2 copies of a mutant allele (gene) is needed to influence the phenotype. aa=show. Aa=carrier, does not display phenotype.

Question 5

What is lyonization?

Answer 5

The inactivation of an X chromosome. One of the two X chromosomes in every female cell is randomly inactivated early in embryonic development.

Question 6

Do unaffected males transmit an X-linked recessive gene.

Answer 6

No. They are not carriers, so they cannot transmit the trait.

Question 7

If you are a female, you got your X chromosome from your mother. What chromosome do you get from your father?

Answer 7

X chromosome.

Question 8

If you are a male, you got your X chromosome from your mother. What chromosome do you get from your father?

Answer 8

Y chromosome.

Question 9

In X-linked recessive, why are all daughters of affected males heterozygous carriers?

Answer 9

-X (from mom)
-X (from dad, with the disease)
Dads disease on the X is recessive. You are “saved” by your moms X chromosome, but still a heterozygous carrier. Since you are a carrier, you can transmit this disease allele to 50% of sons and 50% of daughters.

Question 10

Do fathers ever transmit their X-linked recessive disease to sons?

Answer 10

No. Sons get X from mom and Y from dad so they never get the diseased X from dad. Only the daughter could because dad gives daughter his X.

Question 11

What is unique about mtDNA and its repair?

Answer 11

mtDNA does not have any introns. mtDNA is inherited only through the maternal line. The mutation rate is 10x higher than nDNA. There are no repair mechanisms. Damage from free O2 from Oxphos.

Question 12

If there is a mitochondrial disease, how many of her progeny get it?

Answer 12

All of them because mtDNA is inherited only through the maternal line.

Question 13

At cell division, mitochondria aren’t distributed equally…how does this affect disease?

Answer 13

When the level of mutant mitochondria exceeds a certain threshold, say 80%, the cell expresses dysfunction. If you have an intermediate amount of mutation, you have mild mitochondrial disease.

Question 14

What mitochondrial disorder is caused by one of 3 point mutations affecting NADH dehydrogenase?

Answer 14

Lebers hereditary optic neuropathy (LHON). Causes degeneration of retinal ganglion cells (RGCs) because they are starved of energy and cant send signals to brain. Causes acute or subacute loss of central vision in early teens or 20s.

Question 15

Where is lysine needed in oxphos?

Answer 15

Lysine is required for cytochrome-C oxidase function

Question 16

Myoclonic epilepsy and ragged red fibers (MERRF) is caused by ___?

Answer 16

MERRF is caused by a mutation in the gene encoding for tRNA for lysince, which disrupts the synthesis of cytochrome-c oxidase.

Question 17

Sx or MERRF

Answer 17

Ataxia and seizure. Large variability in presentation due to heteroplasmy.

Question 18

Most commonly inherited mitochondrial disorder

Answer 18

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)
Affects many body systems

Question 19

What causes MELAS?

Answer 19

A single point mutation resulting in lactic acid buildup due to the inability to utilize pyruvate.

Question 20

example of X-linked dominant disorder

Answer 20

Hypophosphatemia.

Question 21

Define euploid

Answer 21

Cells with the normal number of chromosomes

Question 22

Define polyploidy

Answer 22

Cells contain a complete set of extra chromosomes. Often seen in plants.

Question 23

Define aneuploidy

Answer 23

Cells have a missing or an additional individual chromosome. Trisomy, monosomy.

Question 24

What are the 4 types of chromosomal mutations?

Answer 24

Inversion
Deletion
Duplication
Translocation

Question 25

What are the 2 types of translocation mutations

Answer 25

1. Reciprocal: Exchange of material between nonhomologous chromosomes
2. Robertsonian: The long arms of two chromosomes are combines. The short arms are lost.

Question 26

What does karyotyping lack?

Answer 26

It lacks information at the molecular level. But it is the gold standard used in identifying several chromosomal abnormalities associated w/ genetic disorders.

Question 27

What are the 2 syndromes associated w/ a deletion within the chromosome 15 region?

Answer 27

Prader-Willi and Angelman Syndromes. The phenotype depends on if the deletion is on the maternal or the maternal chromosome.
Paternal: Prader-Willi
Maternal: Angelman

Question 28

How does the variability of X numbers influence Klinefelters syndrome?

Answer 28

The more X (48 XXXY, 49 XXXXY) the more severe the symptoms.

Question 29

Sx of Trisomy 18

Answer 29

Edwards Syndrome (47, XX +18)
Microencephaly, prominent occiput, low set ears, smallmouth and jaw, cleft lip/palate, overlapped fingers

Question 30

Sx of Trisomy 13

Answer 30

Patau Syndrome (47, XX +13)
Severe developmental abnormalities, heart and kidney abnormalities, CNS dysfunction, cleft lip, microcephaly.

Question 31

What does 100% penetrance mean

Answer 31

The frequency in which a gene manifests itself. Ex. Retinoblastoma: phenotype occurs in 90% of individuals so there is a 90% penetrance.

Question 32

Examples of variable expressivity?

Answer 32

Neurofibromatosis

Marfan Syndrome

Question 33

What disease is associated with locus heterogeneity

Answer 33

Osteogenesis imperfecta. Locus heterogeneity is when a single disorder, trait, or pattern of traits is caused by mutations in genes at different chromosomal loci. Only 1 mutant locus is needed for phenotype expressivity.

Question 34

Independence

Answer 34

the occurrence of 1 does not affect the probability of occurrence of another. Ex. having a first child boy, second child girl. It’s always 50/50.

Question 35

Multiplication Rule

Answer 35

the probability of a given outcome in multiple trials is the product of the probabilities of each trial outcome

Probability of producing 3 girls: 1/2x1/2x1/2=1/8

Question 36

Addition Rule

Answer 36

probability of either one outcome or another is the sum of the two probabilities

Probability of producing either 3 girls or 3 boys: 1/8 + 1/8 = 1/4

Question 37

Hardy-Weinberg Equation

Answer 37

p^2+2pq+q^2 = 1

Question 38

What kind of disorder is more likely with consanguineous mating?

Answer 38

Autosomal recessive disorders

Question 39

Polygenic

Answer 39

Traits in which variations are thought to be caused by the combined effects of multiple genes

Question 40

Multifactorial

Answer 40

When environmental factors cause variations in the trait

Question 41

What is the threshold of liability?

Answer 41

Occurs in multifactorial resistance. It must be crossed before the disease is expressed.

Question 42

How is sex related to multifactorial resistance?

Answer 42

The least affected sex has a HIGHER risk threshold ( you must have more additive factors than the more affected sex) and transmits the condition more often to the more affected sex because they have a LOWER risk threshold (need fewer factors to show disease)

Question 43

Is pyloric stenosis more common in males or females?

Answer 43

Males. They need fewer risk genes to show disease.

Question 44

What is recurrence risk?

Answer 44

The risk of multifactorial diseases recurring. It differs in populations because gene frequencies and environmental factors differ.

Question 45

When is recurrence risk higher?

Answer 45

1. More than one family member affected
2. If the expression of disease in the proband is more severe
3. If the proband is of the less commonly affected sex