Molecular Genetics Flashcards
Name 4 control points for gene expression in the cell.
- Chromatin Structure, 2. Transcription, 3. Splicing, 4. Translation
What are the four bases for DNA?
Pyrimidines: CYTOSINE and THYMINE; Purines: GUANINE and ADENINE
What is thymine’s RNA equivalent?
Uracil
Which bases pair with each other?
Adenine:Thymine and Cytosine:Guanine
What is a chromosome made up (breakdown of the structure)?
DNA wraps around histones = nucleosome; nucleosomes (beads on a string) pack together = chromatin fiber; condensed chromatin fiber = heterochromatin; condensed heterochromatin = compacted chromosome.
What direction is DNA transcribed?
New DNA is made in the 5’ to 3’ direction. Template strand read in the 3’ to 5’ direction
What is mitosis?
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.
What is meiosis?
Meiosis occurs only in cells of the germline. It results in the formation of reproductive cells (gametes), each of which has only 23 chromosomes.
What are missense mutations?
nucleotide point mutation that results in amino acid substitution
What percentage of disease-causing mutations are missense mutations?
50%
What are nonsense mutations?
nucleotide point mutation that results in a premature stop codon
What percentage of disease-causing mutations are nonsense mutations?
10-12%
What is a frameshift mutation?
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
Large deletions are common in which disorders?
Duchenne muscular dystrophy (dystrophin gene on X chromosome); NF1 (neurofibromin gene)
[Deletions are present in more than 60% of cases]
Name 4 disorders related to trinucleotide repeat expansions and their repeat?
- Fragile X - CGG
- Friedreich ataxia - GAA
- Huntington disease - CAG
- Myotonic dystrophy - CTG
PCR testing can be used to detect what type of disorders?
Trinucleotide repeat expansion disorders
(Allele specific PCR is different and can be used to detect single nucleotide variants like with common cystic fibrosis mutations.)
What are some types of polymorphism?
SNP (single nucleotide polymorphisms), CNV (copy number variants), STR (short tandem repeats), VNTR (variable number tandem repeat), RFLP (restriction fragment length polymorphisms)
How many repeats of CAG are found in the HD gene of individuals affected with Huntington disease?
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
How many repeats of CGG are found in the FMR1 gene of individuals affect with Fragile X?
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
How many repeats of CTG are found in the DMPK gene of individuals affected with myotonic dystrophy?
80-2000 repeats in the 3’ untranslated region (50-80 repeats may be mildly affected)
normal <30
How many repeats of AGG are found in the FRDA gene of individuals affected with Friedreich ataxia?
36-100 repeats in the intronic region (intermediate)
>100 affected
normal <34
What is a dominant negative mutation?
mutation in which the gene product of one allele exerts an inhibitory effect on the function of the system
What is Haldane’s rule?
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)
Humans have approximately how many genes?
25,000
What is the central dogma of molecular genetics?
DNA is transcribed to RNA which is translated to protein.
True/False: introns are transcribed but not translated
TRUE
Clustered repeats make up what percentage of all DNA?
10-15% - centromeres, stalks, satellites
What are some common techniques utilized in molecular testing?
Restriction enzyme digestion, southern blotting, PCR, direct sequencing
GOAL: analyze base pairs
What is genetic polymorphism?
occurrence of multiple alleles at a locus where at least two alleles appear with frequencies >1%
What are polymorphic loci?
loci at which 2% of the population are heterozygotes
What are rare variants?
Alleles with frequences of <1%; most (but not all) deleterious mutations that lead to genetic disease are rare variants
What are RNA processing mutations?
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
What percentage of genetic disease is cause by RNA processing mutations?
10%
What are regulatory mutations?
point mutations that affect transcription factor binding, transcriptional control, or other aspects of gene expression
What are genocopies?
diseases that are caused by the same mutation, but which do not look the same clinically (ie: mito spectrum diseases)
What are phenocopies?
different mutations lead to the same disease (ie: TSC)
