Molecular Genetics

Question 1

Name 4 control points for gene expression in the cell.

Answer 1

1. Chromatin Structure, 2. Transcription, 3. Splicing, 4. Translation

Question 2

What are the four bases for DNA?

Answer 2

Pyrimidines: CYTOSINE and THYMINE; Purines: GUANINE and ADENINE

Question 3

What is thymine’s RNA equivalent?

Answer 3

Uracil

Question 4

Which bases pair with each other?

Answer 4

Adenine:Thymine and Cytosine:Guanine

Question 5

What is a chromosome made up (breakdown of the structure)?

Answer 5

DNA wraps around histones = nucleosome; nucleosomes (beads on a string) pack together = chromatin fiber; condensed chromatin fiber = heterochromatin; condensed heterochromatin = compacted chromosome.

Question 6

What direction is DNA transcribed?

Answer 6

New DNA is made in the 5’ to 3’ direction. Template strand read in the 3’ to 5’ direction

Question 7

What is mitosis?

Answer 7

Mitosis is ordinary somatic cell division, by which the body grows, differentiates, and effects tissue regeneration. Normally results in two daughter cells, each with chromosomes and genes identical to those of the parent cell. There may be dozens or even hundreds of successive mitoses in a lineage of somatic cells.

Question 8

What is meiosis?

Answer 8

Meiosis occurs only in cells of the germline. It results in the formation of reproductive cells (gametes), each of which has only 23 chromosomes.

Question 9

What are missense mutations?

Answer 9

nucleotide point mutation that results in amino acid substitution

Question 10

What percentage of disease-causing mutations are missense mutations?

Answer 10

50%

Question 11

What are nonsense mutations?

Answer 11

nucleotide point mutation that results in a premature stop codon

Question 12

What percentage of disease-causing mutations are nonsense mutations?

Answer 12

10-12%

Question 13

What is a frameshift mutation?

Answer 13

Deletion or insertion of a small number of base pairs (not multiple of 3) in the coding sequence that alters the reading frame beginning at the point of the insertion or deletion

Question 14

Large deletions are common in which disorders?

Answer 14

Duchenne muscular dystrophy (dystrophin gene on X chromosome); NF1 (neurofibromin gene)

[Deletions are present in more than 60% of cases]

Question 15

Name 4 disorders related to trinucleotide repeat expansions and their repeat?

Answer 15

1. Fragile X - CGG
2. Friedreich ataxia - GAA
3. Huntington disease - CAG
4. Myotonic dystrophy - CTG

Question 16

PCR testing can be used to detect what type of disorders?

Answer 16

Trinucleotide repeat expansion disorders

(Allele specific PCR is different and can be used to detect single nucleotide variants like with common cystic fibrosis mutations.)

Question 17

What are some types of polymorphism?

Answer 17

SNP (single nucleotide polymorphisms), CNV (copy number variants), STR (short tandem repeats), VNTR (variable number tandem repeat), RFLP (restriction fragment length polymorphisms)

Question 18

How many repeats of CAG are found in the HD gene of individuals affected with Huntington disease?

Answer 18

36 or more repeats in the coding region (36-39 is usually affected, more than 40 is affected)

normal <36

good table in T&T p 140

Question 19

How many repeats of CGG are found in the FMR1 gene of individuals affect with Fragile X?

Answer 19

more than 200 repeats in the 5’ untranslated region (60-200 is intermediate an individuals may have tremor ataxia syndrome or premature ovarian failure)

normal <60

Question 20

How many repeats of CTG are found in the DMPK gene of individuals affected with myotonic dystrophy?

Answer 20

80-2000 repeats in the 3’ untranslated region (50-80 repeats may be mildly affected)

normal <30

Question 21

How many repeats of AGG are found in the FRDA gene of individuals affected with Friedreich ataxia?

Answer 21

36-100 repeats in the intronic region (intermediate)
>100 affected

normal <34

Question 22

What is a dominant negative mutation?

Answer 22

mutation in which the gene product of one allele exerts an inhibitory effect on the function of the system

Question 23

What is Haldane’s rule?

Answer 23

applies to lethal X-linked recessive conditions; 1/3 de novo mutations and 2/3 carrier mothers

does not apply to non-lethal conditions (ie Hemophilia A 20% new mutations, 80% carrier mothers)

Question 24

Humans have approximately how many genes?

Answer 24

25,000

Question 25

What is the central dogma of molecular genetics?

Answer 25

DNA is transcribed to RNA which is translated to protein.

Question 26

True/False: introns are transcribed but not translated

Answer 26

TRUE

Question 27

Clustered repeats make up what percentage of all DNA?

Answer 27

10-15% - centromeres, stalks, satellites

Question 28

What are some common techniques utilized in molecular testing?

Answer 28

Restriction enzyme digestion, southern blotting, PCR, direct sequencing

GOAL: analyze base pairs

Question 29

What is genetic polymorphism?

Answer 29

occurrence of multiple alleles at a locus where at least two alleles appear with frequencies >1%

Question 30

What are polymorphic loci?

Answer 30

loci at which 2% of the population are heterozygotes

Question 31

What are rare variants?

Answer 31

Alleles with frequences of <1%; most (but not all) deleterious mutations that lead to genetic disease are rare variants

Question 32

What are RNA processing mutations?

Answer 32

point mutations that destroy consensus splice sites, cap sites, polyadenylation sites or create cryptic splice sites; abnormal splicing often leads to frameshift mutations (FS) and premature stop codons

Question 33

What percentage of genetic disease is cause by RNA processing mutations?

Answer 33

10%

Question 34

What are regulatory mutations?

Answer 34

point mutations that affect transcription factor binding, transcriptional control, or other aspects of gene expression

Question 35

What are genocopies?

Answer 35

diseases that are caused by the same mutation, but which do not look the same clinically (ie: mito spectrum diseases)

Question 36

What are phenocopies?

Answer 36

different mutations lead to the same disease (ie: TSC)