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
SNPs and other mutations were thought to be the sole cause of human variation, was this assumption correct?
NO – SNPs are not responsible by themselves for humanities large variation phenotypic expression.
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?
mtDNA changes at a fairly constant rate over time (allowing for aging estimation) while Y chromosome DNA changes/SNP occur in a sequential manner over generations (helps determine when people encountered new areas through migration).
What are the three main problems with trying to determine the cause vs. correlation in genetic disease with genetic studies like the GWAS?
Chance, linkage, stratification
Know the 5 points of control and how they work.
Chromatin, transcription, translation, post-translation into cytoplasm, post-translation modification.
TATA and CCAAT boxes are examples of what.
Promoters
What is exon shuffling, and which part exon or intron remains as a section of the mRNA?
Exons are a segment of DNA that code for a particular protein/peptide sequence.
Exons remain as section of mRNA.
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?
Methyl group
When looking at a cartoon or ideogram of a chromosome, how can you tell the locus from the gene?
Locus: indicated by p or q
Gene: usually acronyms given by their discoverer
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
5 basic modes of inheritance?
Autosomal dominant Autosomal recessive X-linked dominant X-linked recessive Mitochondrial
What did the story about Koko and her kitty cat suggest about human behavior?
Behaviors like deception are likely inherited traits from the animal kingdom.
Disease and pedigree characteristics of autosomal dominance?
Person needs only 1 copy of the gene or the allele to be mutant in order to have the trait, characteristic, or disease to be expressed.
Expressed in every generation.
Disease and pedigree characteristics of autosomal recessiveness?
Person needs to have 2 copies of the gene or allele to be mutant in order to have the trait, characteristic, or disease to be expressed.
Typically observed in only 1 generation of a pedigree (may skip).
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)
Why can males get X-linked recessive diseases with just one mutated allele? (Normally two disease alleles are needed to manifest a recessive disease)?
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.
Nonsense – a base change that results in a “stop codon” – a short and completely inactive protein/enzyme.
What is the difference between a gain-of-function and a loss-of-function mutation, and is one necessarily less troublesome than the other?
Loss-of- function: causes a vital or protective protein to become non-functional in the cell (e.g. loss of tumor suppressors leads to cancer).
Gain-of-function: occur when either a completely new enzyme is produced in a cell, or more commonly, the enzyme is over-produced (e.g. proto-oncogenes become oncogenes).
Loss of function are more commonly associated with severe diseases.
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 (higher number of CGG repeats = greater severity).
Name is due to one arm of the X chromosome a-danglin’.
What is the epigenetic significance of X Chromosome inactivation, and what is a barr body?
One of the x-chromosomes in females is made inactive because if both were active they would overproduce proteins/enzymes made from x-chromosomes. The inactivated x-chromosome becomes a barr body.
Epigenetic significance = ??
What is the general clinical characteristic of inherited mitochondrial disease?
Neuropathies and/or myopathies
What is the difference between penetrance, incomplete penetrance and variability?
Penetrance – the degree to which the disease genotype is expressed.
Incomplete penetrance – when some people with the disease genotypes do not express the disease phenotype.
Variability = how “bad” the disease is when it is expressed.
What is recurrence risk (RR) and how is it calculated?
RR = penetrance X 25% (AR) or 50% (AD)
What is pleiotropy? Is Marfan syndrome an example?
Pleiotropy - a single mutation affects multiple organ systems..
YES - Marfan Syndrome is an AD mutation in fibrillin which causes issues in many organ systems, (1/10,000)
What is anticipation? What does it imply will occur in each subsequent generation of a family carrying a mutation causing a disease characterized by anticipation?
A pattern of inheritance in which individuals in the most recent generations of a pedigree develop a disease at an earlier age or with greater severity than do those in the earlier generations (Huntington dz).
How are the bands of a chromosome stained for a karyotype? What are the 3 types of bands that appear after staining?
Glemsa staining reveals POSITIVE, NEGATIVE, or VARIABLE bands.
How many base pairs have to be involved in a deletion or duplication to be grossly detectable on a karyotype without using special immunofluorescent stains?
If the deletion is smaller than this number, can a FISH study be used to detect it?
Differences >4 Mb can be seen
< 4Mb requires detection by FISH
What is the main cause of NUMERICAL chromosome abnormalities?
Meiotic nondisjunction due to spindle fibers behaving badly.
What are the names for trisomy 21, 18, and 13?
21: Down Syndrome
18: Edward Syndrome
13: Patau Syndrome
Why aren’t there any autosomal monosomies listed in the slides?
They are incompatible with life.
Characteristics and karyotype number for Turner syndrome?
Turners (45X): short stature, ovarian dysgenesis, and neurocognitive problems. Only monosomy consistent with life, because not autosomal.
Through which mechanism is the Philadelphia chromosome formed? What is its significance in terms of the disease it is most often associated with?
Philadelphia chromosome is formed by reciprocal translocation of chromosomes 9 and 22 and is associated with chronic myelogenous leukemia.
Can partial monosomies occur? What would the karyotype of Down syndrome caused by a partial monosomy read?
Yes.
46,XX,-14,+t(14q;21q) or 46,XY,- 14,+(14q;21q)
Rather than: 47,XX,+21 or
47,XY,+21
Characteristics and karyotype number Klinefelter syndrome?
Klinefelter’s (47XXY), “hermaphrodite disorder”: mostly male phenotype, low T and elevated LH:FSH common, taller than average.
Characteristics and karyotype number XYY?
Alien 3 syndrome (47XYY): normal, tall stature (not violent as depicted in movies).
Through which mechanism is the Philadelphia chromosome formed? What is its significance in terms of the disease it is most often associated with? How it will read on a karyotype {i.e. something like t(8;25) } or whatever the Philadelphia chromosome numbers are?
Philadelphia chromosome is formed by Reciprocal translocation of chromosomes 9 and 22 and is associated with CML
(t9;22)
Cri-du-chat results from what abnormality? Does the patient’s voice improve as they age?
caused by deletion on short arm of chromosome 5 leading to abnormal larynx development
most develop normally after age 2
What’s going on in Angelman Syndrome?
a micro-deletion of maternal 15, causing happy children who are ataxic and epileptic
What’s going on in Prader-Willi Syndrome?
Prader-Willi Syndrome – microdeletion in paternal chromosome 15, causing child who intensely craves food and floppy baby
What is a ring chromosome, and what is its significance? How will it read on a karyotype?
A ring chromosome forms when a deletion occurs on both tips of a chromosome and the remaining chromosome ends fuse together, often resulting in a monosomy
r – ring chromosome
t – translocation
i – isochromosome
What are isochromosomes, and are they seen in the autosomes in live patients?
A chromosome divides along the axis perpendicular to its normal axis of division resulting in two copies of one chromosome, but no copy of the other
Autosomal isochromosomes are incompatible with life, most observed in live births involve the X chromosome
1) When is it thought that these epigenetic effects are imprinted onto the fetus’s of women 2) When can the influence be acquired for transmission by the males.
1) in utero
2) anytime
Not the only times epigenetic effects can be acquired or passed on. doy.
Did studies performed in mice performed at the world renowned - and prestigious - Washington State University in Pullman, demonstrate the cancer causing heritable changes in mice were not a result from a sequence change in the DNA itself?
I dunno
What are the major reasons gene therapy did not work out well.
Infecting gene via virus into humans can be very challenging and potentially harmful
What is iRNA?
Interference RNA - inhibits gene expression or translation by neutralizing targeted mRNA
Can iRNA be passed to subsequent generations?
Yes. Pretty sure…
What are knock-down studies? How do they work? What do they tell you about a gene? What is the most effective modality for performing knock-down studies?
Gene knockdown is an experimental technique by which the expression of one or more of an organism’s genes are reduced. The reduction can occur either through genetic modification or by treatment with a reagent such as a short DNA or RNA oligonucleotide that has a sequence complementary to either gene or an mRNA transcript.
Interference RNA
Who was George price and what was his contribution to genetics?
first, rederiving W.D. Hamilton’s work on kin selection with a new Price equation that vindicated group selection; second, introducing (with John Maynard Smith) the concept of the evolutionarily stable strategy (ESS), a central concept in game theory; and third, formalizing Fisher’s fundamental theorem of natural selection. Got it?
