Molecular Genetics

Question 2

What are the 4 types of mutations?

Answer 2

Point, frameshift, trinucleotide repeat, and splicing.

Question 3

Mutations

Answer 3

Permanent changes in DNA

Question 4

What are the twp types of point mutations?

Answer 4

Missense (substitution) and nonsense (mutate to stop codon)

Question 5

What are frameshift mutations?

Answer 5

Deletion or insertion of >=1 nucleotide that changes the reading frame

Question 6

What are trinucleotide repeats?

Answer 6

Amplification of the same 3 nucleotides (usually involve CG)

Question 7

What is splicing?

Answer 7

Affects the structure or abundance of mRNA (point or frameshift w/I exons or introns)

Question 8

List the 4 types of Mendelian Inheritance?

Answer 8

1) Autosomal recessive, 2) autosomal dominant, 3) X-inked recessive, 4) X-linked dominant

Question 9

List some uncommon characteristics of autosomal recessive traits:

Answer 9

New mutations are rarely clinically detected, enzymes are effected, and complete penetrance is common; if mutation is rare, disease may occur through consanguinity.

Question 10

List some examples of autosomal recessive diseases:

Answer 10

CF, PKY, galactosemia, Tay-Sachs, mucopolysaccharidoses.

Question 11

List some uncommon characteristics of autosomal dominant traits:

Answer 11

New mutations are detected clinically, and clinical features can be modified by reduced penetrance and variable expressivity. Regulator and structural proteins are no affected.

Question 12

List some examples of autosomal dominant diseases:

Answer 12

Familial hypercholesterolemia, marfan syndrome, Ehler-Danlos syndrome.

Question 13

List one uncommon characteristic of X-linked recessive traits:

Answer 13

Heterozygous females can express them via X-inactivation.

Question 14

What are triplet repeat expansions?

Answer 14

Usually involved in neurodegenerative disorders and usually include CGs. Cause loss of protein function (CCG in Fragile X) or a gain of function (CAG in Huntington’s)

Question 15

What does it mean when triplet repeat expansions are dynamic?

Answer 15

When a certain threshold of repeats is met (51), the premutation-stage begins and gametogenesis leads to full-mutation.

Question 16

What is Fragile X syndrome?

Answer 16

Mutation in FMR1 gene causes mental retardation.

Question 17

How does Fragile X differ from classical X-linked recessive?

Answer 17

Some males are clinically normal and can transmit their mutations to grandsons through their phenotypically normal daughters (pre-mutation carriers). About 50% of female carriers are mentally retarded (full mutation carriers).

Question 18

What is mitochondrial inheritance?

Answer 18

Mutations are rare, and all mitochondria are maternal. Ova have many mitochondria and spermatozoa have few.

Question 19

What are the 5 types of atypical/non-mendelian forms of inheritance?

Answer 19

Triplet-repeat expansions, mitochondrial inheritance, and genomic imprinting,

Question 20

What is genomic imprinting?

Answer 20

It’s epigenetic modifications; to imprint means to silence those genes. Since only one copy of a gene can exist, then homogyous diseases can take place.

Question 21

What is Prader-Willi syndrome?

Answer 21

Localized to chromosome 15 and results from disruption of paternally inherited diseases.

Question 22

What is Angelman syndrome?

Answer 22

Localized to chromosome 15 and results form the disruption of materally inherited genes. Can also result from mutation in paternally-imprinted UBE3A ligase gene.

Question 23

What types of gene disruptions are common to both PWS and AS?

Answer 23

Deletion up to several megabases, uniparental inheritance (both chs from 1 parent), and abnormal methylation.

Question 24

What are three techniques to diagnose genetic disease?

Answer 24

Chromosome analysis, PCR, and linkage analysis

Question 25

What are three types of chromosome analyses techniques?

Answer 25

Banding/karyotype, FISH, and microarrays.

Question 26

Describe chromosome banding/karyotyping. What is it useful for?

Answer 26

Low resolution analysis of metaphase to identify numerical and structural chromosomal abnormalities.

Question 27

Describe FISH (fluorescence in situ hybridization). What is it useful for?

Answer 27

Hybridize chromosomes/gene-specific DNA probes to complimentary DNA sequences of interphase/metaphase cells that are labelled. The size of the change detected depends on the size of the probe. Useful for detecting structual/numerical changes using a few probes per each hybridization.

Question 28

Describe microarray hybridization. What is it useful for?

Answer 28

Hybridizes labelled DNA to many probes. Useful for copy number gains and losses, as well as regions of homozygosity and uniparently disomy if SNP probes are included. Do not provide chromosomal context.

Question 29

When is PCR used and what is it useful for?

Answer 29

Usually used when mutations cannot be detected via microarrays/FISH/banding. If RNA is used, it is taken from lymphocytes and transcribed to cDNA by PCR. Requires knowledge or normal gene and different mutations. Abnormalities can be detected via direct sequencing, restriction enzyme digestion, allele-specific extension, etc.

Question 30

When is linkage analysis used?

Answer 30

When gene is not known or polygenic. It involves examining the inheritance of marker loci in family members and identifying a set of loci (haplotypes) that co-segregate with the disease. Depends on SNPs.