Mendelian and non-Mendelian 2

Question 1

Anticipation

w/ regards to trinucleotide repeats

Answer 1

• increased severity or earlier onset of a phenotype with each successive generation
• this is caused by specific areas of instability in the genome, such as trinucleotide repeats

Question 2

trinucleotide repeats
copy number variation
clinical correlate

Answer 2

• present throughout the genome and are usually stable during mitosis and meiosis.
• copy number is transmitted as a polymorphism
• there can be a direct correlate between copy number and severity of a disease process

Question 3

Mosaicism definition

-what type of mutations cause this

Answer 3

-the presence of more than one genetically distinct cel within an organism

Question 4

Somatic mosaicism

Answer 4

• mosaicism in non-gamete cells
• usually cuased by a post-zygotic mutation which can effect a certain percentage of the cells in one or more tissues
• variable degrees of disease severity
• depends on the percentage of mutated cells in each tissue

Question 5

examples of mosaicism:
downs
cancer
pallister-killian

Answer 5

• downs: some somatic cels have 3 chromosome 21’s while pther do not. phenotype is impossible to predict but could be less severe
• cancer: certain cells acquire a mutation that cuases tumor growth, all daughter cells will have the mutation

Question 6

gonadal mosaicism

• definition
• how it occurs
• phenotype
• testing
• subsequent children after discover
• identifying in pedigree

Answer 6

• the presence of a mutation in some or all of the germ cells
• a sperm or egg cell acquired a mutation at some point
• the person with mutated germ cells will not show a phenotype
• not possible to test sperm or egg cells for a mutation
• emperic risk assessment for subsequent children after disease is discovered
• strongy suspect when two or more children are effected with a dominant disorder and the parents are not

Question 7

genomic imprinting:
cause
definition
results
uniparental disomy and het mutations/deletions

Answer 7

• the different epigenetic modification of the maternal and paternal genetic contributions to the zygote
• some genes are expressed preferantially from the maternal and paternal alleles
• results in differences in gene expression and phenotype depending on if the gene has been inherited from mom or dad
• can lead to difference in phenotype if a pteient has uniparental disomy or a heterozygous deletion/mutation for an imprinted region of a chromosome

Question 8

mechanism of imprinting

Answer 8

• methylation of DNA plays an important role
• selective methylation occurs before and or around the time of fertilization
• methylation confers transcriptional silencing
• is reversible on passage through the germ line (if a gene is maternally imprinted and the child is a male, that gene will not be found on the other chormosome)

Question 9

prader-willi syndrom
symptoms
causes
neumoic

Answer 9

-hypotonia, intellectual disability, and hyperphagia (overeating)
-due to lack of expression of critical regions normally expressed from the maternal allele
-could be due to gonadal mosaicism, the gene is deleted in the fathers sperm
-uniparental disomy of chromosome 15 from the mother could also cause this
prader no father

Question 10

Angelman’s syndrome
symptoms
causes, one rare
neumonic

Answer 10

-severe mental disability, movement disorders, and seizure
-caused by lack of expression of genes in the critical region normally expressed from the maternal allel
-could be due to a deletion in the maternal chromosome
-could be due to uniparental disomy of chromosome 15 from the father
-rarely, mutations in the maternally inherited UBE3A gene result in Angelman’s syndrom
mommy’s little angel

Question 11

uniparental dismoy

Answer 11

• the presence of two homologous chromosome inherited by one parent
• could be all or part of the chromosome

Question 12

heterodisomy

Answer 12

-as a result of nondisjunction in meiosis 1, the parent contributes one copy of each homologous chromosome

Question 13

isodisome

Answer 13

-as a result of nondisjunction in meiosis 2, if the parent passes on two IDENTICAL copies of the same chromosome

Question 14

when is uniparental disomy clinically significant

Answer 14

• when it involves chromosomes with imprinted genes. This is because if gene was readily used from wither parents chromosome, the child would be fine
• considered when a child is affected with an autosomal recessive disorder for which only one parent is the carrier

Question 15

proposed mechanism for uniparental disomy

Answer 15

• a trisomic conception with a subsequent post zygotic deletion of one chromosome
• fertilization of a nullisomic gamete by a disomic gamte
• compensatory of the chromosome in a monosomic cell