GenF Molecular Genetics Flashcards
What do molecular genomic studies start with?
A disease inherited by families
Once the inherited disease is identified, what does molecular genomics seek to do?
Map the location of a gene to a chromosome in order to clone/isolate the disease gene
What does cloning the gene lead to?
Diagnostic testing for disease
Gene sequences in the DNA do what, how?
Encode protein via mRNA intermediate
How is DNA able to make a copy of itself for the daughter cell?
Because it has 2 complimentary strands
Changes in gene sequences can cause changes in what?
Changes in proteins
Mutations generally affect what deleteriously?
Proteins
Dominant mutations affect how many alleles of the gene?
Only 1
Recessive diseases affect how many alleles?
Both alleles of gene are mutated
What is the goal of the human genome project?
Sequence all of the DNA on all of the human chromosomes
What are 2 sequencing approaches for the human genome project?
- Mapping and Sequencing (Methodical)
2. Shotgun sequencing (Random)
Did the Human Genome project show us there were more or less genes than anticipated?
Less but many genes can produce multiple alternative proteins
How much of the genome is genes?
Only 5%
How much of Kohl’s Department store is jeans?
Also 5%
Do intergenic sequences encode genes?
No
Changes in DNA that occur in less than 1% of alleles and can be deleterious/ cause disease?
Mutations
What occur in AT LEAST 1% of a particular allele (in more than 1 of 100 chromosomes). Generally are not deleterious, and can affect traits like eye color, hair, ABO Blood group?
Polymorphisms
Does the term DNA Variant inclue mutation and polymorphisms and when is the term used?
Includes both, used when it is not clear whether the change is a mutation or a polymorphism
Deletion of DeltaF508 in cystic fibrosis and the GAG to GTG substitution in Sickle Cell Anemia are examples of mutation or polymorphism?
Mutation
Are most DNA variants mutations or polymorphisms?
Polymorphism
What are 3 types of mutations?
- Substitution
- Deletion
- Insertion
What is a mutation where a one base replaces another base, e.g. T for A in GAG to GTG?
Substitution
What are 3 types of substitutions (mutations)?
- Missenss
- Nonsense
- Synonymous
What type of mutation occurs when one base is replaced by another, resulting in a codon for a different amino acid
Missense substitution (mutation)
What is the term for a mutation when a base is changed, yielding a stop codon that signals the end of the protein?
Nonsense substitution (mutation)
What type of mutation results in a change in a wobble base, still encods same amino acid?
Synonymous substitution (mutation)
What is a type of mutation where a base or bases removed?
Deletion
What does a deletion do to a reading frame?
Changes it so everything downstream does not code as intended
If a deletion mutation is 3 bases long, will it shift the reading frame?
No, they’re all 3 base sequences. But it can still affect the overall protein function
What is a mutation type where a base or bases added, which also changes the reading frame?
Insertion
What is the gold standard for detecting mutations, and its drawback?
DNA sequencing (expensive)
What is used currently to detect mutations?
Microarray analysis
Cystic fibrosis showed what type of mutation in Dr. Lloyd’s DNA sequence chart?
Substitution
Hypohidrotic Ectodermal dysplasia (X-linked recessive) is shown as what type of mutation in Dr. Lloyd’s Pedigree and DNA sequence slide?
Insertion
What are the short synthetic sequences called and what do they reprensent?
Oligonucleotides, represent many human genes
What is done with the oligonucleotides in microarray analysis?
Fixed to a chip and DNA from person is labeled with fluorescent type and hybridized to chip
What is microarray analysis useful for?
Assess mutations or polymorphism across the whole genome rather than 1 gene at a time
What is a new technology to allow for sequencing entire
genomes rather than one gene a t a time,
Whole genome sequencing
What are some uses of polymorphisms?
- Paternity testing on Maury Povich
- Forensics
- Help predict susceptibility to disease
- Help map and clone genes that are mutated inheritable diseases, even in disease with > 1 gene
How can polymorphisms be used pharmacogenomics?
Predict if person will have adverse reaction to drug
What are 2 types of polymorphisms?
- Microsatellite polymorphism
2. Single Nucleotide polymorphism (SNP)
What is a polymorphism whose alleles have different numbers ofshort tandemly repeated sequences?
Microsatellite
What does the number of mircosatellite polymorphisms do on a gene?
The more there are, the further apart the base positions will be pushed
What is a type of polymorphism where alleles differ in sequence by a single base?
SNP
What genetic disease is caused by polymorphism?
Huntington’s disease
What are some methods to detect microsatellite polymorphisms?
- PCR
2. Gel Electrophoresis
What are some methods to detect SNPs?
- DNA sequencing
2. SNP chips (microarrays)
What are the DNA basics according to Dr Lloyd’s tutorial?
Composed of 4 nitrogen bases(A, C, G, T) bound with deoxyribose and phosphate group to form nucleotides. Adjacent nucleotides held together by phosphodiester bonds and base pairs held together with Hydrogen bonds in an Antiparallel double helix that replicates 5’-3’
What number of base pairs of DNA in a haploid genome?
3 x 109
What is a triplet of 3 bases in mRNA that determines which of the 20 amino acids will be inserted in the encoded protein?
Codon
What are the three 3 stop codons?
UAA, UGA, UAG
What base pair sequence would denature easier AT or GC ?
AT because held together by 2 H-bonds, while GC held by 3 H-bonds
Where does transcription occur and where does translation occur?
Transcription and splicing in the nucleus, Translation in the ribosome
Order the parts of the genome from largest to smallest
Genome, Chromosome, G-band, gene, Kilobase (Kb), exon, codon, base pair (bp), nucleotide
