midterm Flashcards
(51 cards)
What was the “one gene hypothesis,”? Did it turn out to be correct?
Genes make proteins – one gene = one protein
NO – 1 gene codes for at least 10 proteins
Alternative splicing- one gene encodes for multiple RNA’s
SNPs and other mutations, were thought to be the sole cause of human variation, was this assumption correct?
NO – humans have minimal gene variation. And variation is due to gene regulation and the epigenome
How much of the Human Genome is protein coding? How much is RVS?
4% protein coding, 10% retroviral
In what people and country does most of the variability in the human genome still reside?
San Bushmen of East Africa
How are mitochondrial DNA and Y chromosome DNA different, and how are they used in migration studies?
Comparing the mtDNA “age” with the number of mutations on the Y chromosome, the time frame and direction of migration can be determined.
mtDNA allows us to estimate the age of a species.
What did the story about Koko and her kitty cat suggest about human behavior?
????
What are the three main problems with trying to determine the cause vs. correlation in genetic disease with genetic studies like the GWAS (slide 27 lecture )
Chance (variant mb found by random chance),
Linkage (study bias- variant is next to the disease causing segment but does nothing on its own),
Stratification (an ethnic group has concentration of the variant and the disease but they aren’t linked).
Know the 5 points of control and how they work
1) Chromatin: Histone methylation. Target sites of histone methylation are cytidines which exist as CG (CpG. Areas with lots of them are CpG islands) Methylation of CpG down regs transcription. Histone acetylation- add an acetyl group, stopf further condensing of DNA- encourages active transcription. Generally methylation upregs transcription and demethylation inhibits. Methyl, Acetyl and Phosphate groups are ones that modify histones.
2) Transcription- Promoters CCATT and TATA boxes. Are in all protein coding genes. Exon shuffling, enhancers (transcription factors bind to enancer regions)
3) Translation- RNA transport (exportins). Importins and exportins are regulated by GTPases called Ran
4) Post-translation into cytoplasm- Cap/ tail communication
5) Post-translation modification
TATA and CCAAT boxes are examples of what (slide 11 lecture 2)
Promoters
What is exon shuffling, and which part exon or intron remains as a section of the mRNA?
EXONS
A molecular mechanism for the formation of new genes. It is a process through which two or moreexonsfrom different genes can be brought together ectopically, or the sameexoncan be duplicated, to create a newexon-intron structure
What is the role of enhancers?
Enhancer - a short (50-1500 bp) region of DNA that can be bound by proteins (activators) to increase the likelihood that transcription of a particular gene
What are the 3 major types of molecular groups that modify histones and cause epigenetic effects?
Methyl, Acetyl, Phosphate
Which epigenetic marker can attach to DNA directly?
METHYLATION
When looking at a cartoon or ideogram of a chromosome, how can you tell the locus from the gene? (essentially know the abbreviations for each. For instance is EPO the gene or the locus? (slide 7 lecture 3)
The locus is marked by a “p” or “q” followed by a number, genes are marked by acronyms given by their discoverer. So EPO is the gene.
What are DNA Marker Alleles? Are they necessarily involved in transcription or biologically active?
Any gene or allele that is associated with a specific chromosome and can be used to identify the chromosome or to locate other genes or alleles
They are not necessarily directly involved in transcription or biologically active
What is the difference between the Genotype and the Phenotype?
Genotype - combination of alleles a person has
Phenotype - any observable trait, expressed by genotype
Know the disease characteristics and pedigree characteristics of the 5 basic modes of inheritance
Autosomal dominant - The locus is on an autosomal chromosome (1-22) and only one mutant allele is required for expression of the phenotype
Autosomal recessive - The locus is on an autosomal chromosome and both alleles must be mutant alleles to express the phenotype
X-linked recessive - The locus is on the X chromosome and both alleles must be mutant alleles to express the phenotype in females. Men can have the disease with only one copy of the gene.
X-linked dominant - The locus is on the X chromosome and only one mutant allele is required for expression of the phenotype in females
Mitochondrial inheritance - The locus is on the mitochondrial “chromosome”
Know the modes of inheritance (i.e. AD, AR, X-linked….. etc.) and what their pedigrees look like (i.e. which show each generation effect, which skip generations)
Dominant will be in all generations. Recessive will skip generations. If males and females are affected equally it is autosomal, if not, is X linked.
AD disease are uncommon. AR disease are common
AD most common trait obviously.
Mitochondrial inheritance cannot come from Dad. Can affect sons and daughters though. All offspring of an affected female are affected.
What are the characteristics of X-linked Dominate diseases? Can they be transmitted from father to son? Can they be transmitted from father to daughter?
X-linked dominant disease are twice as common in females than males, because a father cannot transmit to his son, but only his daughter (father does not give X chromosome to son). X linked dominant can affect males and females.
Dad can give X
Why can males get X-linked recessive diseases with just one mutated allele? (Normally two disease alleles are needed to manifest a recessive disease)? (slide 13 lecture 3)
Males only have one x chromosome.
What is the difference between a missense mutation and a nonsense mutation?
Missense – single base change in the gene that leads to a change in the codon that encodes for one amino acid. Effect depends on which base was subbed.
Nonsense – a base change that results in a “stop codon” – a short and completely inactive protein/enzyme. Severe disease likely.
What is the difference between a gain-of-function and a loss-of-function mutation, and is one necessarily less troublesome than the other? (Think tumor suppressors vs. proto-oncogenes)
“Loss-of- function” - cause a vital or protective protein to become non- functional in the cell (loss of Tumor Suppressors leads to cancer
“Gain-of-function mutations” occur when either a completely new enzyme is produced in a cell, or more commonly, the enzyme is over produced (proto-oncogenes become oncogenes)
Why is consanguinity important in clinical medicine, even though it is rare amongst Americans?
“Kissing Cousins” – can give rise to genetic diseases (recessive). Although 50% of marriages are consanguineous.
Why is it called fragile X syndrome, and what determines its severity?
Most common cause of mental retardation due to a number CGG repeats, which determines severity
