CBCL1: Medical Genetics Chapters 5, 6, 7

Question 1

Missense Mutation

Answer 1

single base change resulting in a change in Amino Acid

Question 2

Nonsense Mutation

Answer 2

Changes base pair to stop codon

->results in premature trunkation of protein, deleterious

Question 3

Frameshift Mutation

Answer 3

insertion or deletion of bases in anything other than multiple of 3
->results in stop codon creation within several codons or unstable protein, deleterious

Question 4

3’ end of Exon ends in:

Answer 4

AG
*Note: Mutation here technically can be “silent” because it doesn’t result in a change in AA, but still can have a phenotypic effect because of an alteration in splicing

Question 5

5’ end of an Intron adjacent to an exon is:

3’ end of an Intron:

Answer 5

GT (splice donor)

AG (splice acceptor)

Question 6

Loss of Function Mutation:

Answer 6

Reduced Amount or Reduced activity of a gene product.

->minimum effect unless homozygous for alleles

Question 7

Recessive Phenotype

Answer 7

Homozygous for a Loss of Function alleles

Question 8

Null Allele

Answer 8

Loss of function allele when Heterozygous for this mutation (the shitty allele)

Question 9

Haploinsufficiency

Answer 9

Heterozygous for Loss of Function alleles, but decrease in levels of gene product results in altered phenotype from mutation in null allele.
–>This altered phenotype is considered a Dominant Phenotype

Question 10

Dominant Phenotype

Answer 10

Phenotype produced when heterozygous for a gene.

–>NOTE*: can be phenotype produced by haploinsufficiency

Question 11

Dosage Sensitivity

Answer 11

a change in phenotype produced from gene A because of insufficient interaction with product of gene b. Insufficient interaction results because of low concentration of product of gene B as a result of haploinsuffiency.

Question 12

Dominant Negative Effect

Answer 12

Heterozygous for Loss of Function mutation and product of mutant allele interferes with product of normal allele
–>typically more severe than loss of product

Question 13

Gain of Function Mutation

Answer 13

Produce an Increased amount or Increased activity of a gene product

• ->Very specific changes allowing for formation of a product with enhanced activity of its existing function or new function
• ->Often missense in specific location OR frameshift expansion in microsatellite repeat areas (CAG triplet expansion = Huntington’s)

Question 14

First Degree Relatives

Answer 14

Parents, Siblings, and children

Question 15

Second Degree Relatives

Answer 15

Grandma/Grandpa, Aunts/Uncles, Nephews/Nieces, half-siblings

Question 16

Third Degree Relatives

Answer 16

First Cousins, Great Grandparents

Question 17

Consanguinity

Answer 17

Blood relationship between descendants of a common ancestor (inbreeding)

Question 18

Autosomal Dominant Inheritance Pattern:

Answer 18

1. Males and Females equally affected
2. Males and Females equally capable of transmitting trait
3. Affected person usually has one affected parent
4. 50% probability of transmitting the trait
   (commonly non-enzymatic protein)`

Question 19

Autosomal Recessive Inheritance

Answer 19

1. Both parents usually asymptomatic carriers
2. M and F equally affected
3. Increased with Inbreeding
4. Unaffected parents with 1 affected child have 25% chance of having another affected child with each pregnancy
5. unaffected siblings have 2/3 risk of being a carrier

Question 20

X-Linked Recessive

Answer 20

1. Affects Males
2. All daughters of affected males are carriers
3. Females are affected if they have an affected father and carrier mother
4. Female carriers have 50% risk of passing it on to son or 50% of having carrier daugher

Question 21

X-Linked Dominant

Answer 21

1. Both Males and Females may be affected
2. Females usually less evident
3. pedigree looks similar to autosomal dominant BUT NO MALE TO MALE TRANSMISSION

Question 22

Mosaicism is caused by:

Answer 22

de novo mutations in parental gamete

–>Often looks like autosomal recessive pedigree

Question 23

Clinical heterogeneity

Answer 23

mutations in same gene produce different clinical disorder

Question 24

Allelic heterogeneity

Answer 24

multiple mutations within the same allele cause the same disorder

Question 25

Locus heterogeneity

Answer 25

mutations at more than one gene locus cause same disease (differs from clinical hetrogeneity cuz on different genes not different mutations in SAME gene)

Question 26

heteroplasmy

Answer 26

mixed normal and abnormal mitochondrial genomes within each cell

Question 27

haplotype

Answer 27

a set of polymorphisms in different genes that reside closely on a given chromosome and are often inherited together. A particular haplotype can correlate with disease severity.