LEC 48 Atypical Inheritance

Question 1

What is somatic mosaicism?

Answer 1

• The presence of one, or more than one, cell population arising from a single zygote by genetic or genomic alterations
• CLINICAL: Some cells have the mutation or chromosome change, not all of them (babies with marbled skin)

Postzygotically occurs (random mutation after fertilization), not inherited in Mendelian way.

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Question 2

What is germ cell mosaicism?

Answer 2

• Mutations occur after conception (POSTZYGOTIC) so it is not inherited in a Mendelian way
• The mutations are located only on some germ cells, parent is asymptomatic, but condition is HERITABLE

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Question 3

What is genomic imprinting?

Answer 3

• differential expression of the paternal versus the maternal DNA
• some genes are normally “silenced” depending on if they are maternal or paternal

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Question 4

Explain the genomic imprinting aspect of Prader-Willi and Angelman syndrome.

How are they aquired?

Answer 4

Prader-Willi: paternal deletion
Angelman: maternal deletion

Deletion on chromosome 15 for both

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Question 5

What are the clinical manifestations of Prader-Willi syndrome?

Answer 5

• congenital hyptonia
• hypogonadism
• intellectual disability - mild to moderate
• obesity (goes from feeding tube to being insatiable)

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Question 6

What are the clinical manifestations of Angelman syndrome?

Answer 6

• (“happy puppet syndrome”)
• Severe intellectual disability
• periods of unprovoked laughter
• absent speech
• microcephaly
• ataxic gait

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Question 7

What is uniparental disomy?

Answer 7

• 2 copies of a particular chromosome from the same parent

Isodisomy=same chromosome; Heterodisomy=different chromosome

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Question 8

What is compound heterozygosity?

Answer 8

The presence of 2 different mutant alleles at a particular gene locus; one on each allele of the pair

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Question 9

What is anticipation?

Answer 9

-the apparent worsening of a disorder with subsequent generations
-trinucleotide repeat disorders

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Question 10

What is fragile X syndrome?

Answer 10

(loss of function)
* X linked intellectual disability
* Expansion of repeat only when transmitted maternally!!
* Trinucleotide repeat = CGG (Normal 6-46)
* Repeat in 5’ untranslated region of FMR1 gene

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Question 11

Describe anticipation with regards to Fragile X syndrome.

Answer 11

• The more repeats that are present, the more likely the expansion in female transmission will exceed 200 repeats.
• Number of affected males increases in successive generations.
• Males as carriers with fewer than 200 repeats will pass the same number of repeats to all their daughters, but those daughters will pass expanded repeats to their offspring.

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Question 12

What is multifactorial inheritance?

Answer 12

• “many factors”
• both genetic & environmental factors have significant contributions to the phenotype
• you could say all genetic conditions are “multifactorial”

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Question 13

What is polygenic inheritance?

Answer 13

• “many genes”
• multiple genes each with an additive effect

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Question 14

What is epigenetic inheritance?

Answer 14

• the transmission of information from a cell or multicellular organism to its descendants without that information being encoded in the nucleotide sequence of the genes
• does not follow the rules of Mendelian inheritance, is often the result of changed gene expression and may be reversible

X-inactivation, imprinting, & DNA methylation

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