Midterm Flashcards
Who was George Price and what was his contribution to genetics?
During
that brief period Price made three lasting contributions to evolutionary theory; these were: (i) the Price
Equation, a profound insight into the nature of selection and the basis for the modern theories of kin
and group selection; (ii) the theory of games and animal behavior, based on the concept of the
evolutionarily stable strategy; and (iii) the modern interpretation of Fisher’s fundamental theorem of
natural selection, Fisher’s theorem being perhaps the most cited and least understood idea in the history
of evolutionary genetics
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 – humans have minimal gene variation
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
Were these mice pregnant or pregnant and in the 3rd trimester when sprayed with pesticides? (ans: NOOOO!) This suggests what about when epigenetic changes can take place?
Epigenetics can take place ANYTIME!!!!
In the Overkalix studies, it was found that nutritional influences and their subsequent epigenetic markers could be transmitted to future generations. 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. Also, are these the only times epigenetic effects can potentially be acquired by a person, and subsequently transmitted to future generations? (ans: NOOOOO!)
Epigenetic effects are imprinted into women when mother is in utero
Epigenetic effects are imprinted into males at any time
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 1)
Chance, linkage, stratification
Know the 5 points of control and how they work
Chromatin, transcription, translation, post-translation into cytoplasm, post-translation modification
What is a ring chromosome, and what is its significance? How will it read on a karyotype? (what I am asking, is what do the letters coming before the chromosome numbers (r, t, i) each mean). For instance, what does this mean à t(9;22)(q34;q11)
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 is exon shuffling, and which part (exon or intron?) remains as a section of the mRNA?
EXONS
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)
Locus is the location of the gene, abbreviated by p or q and a number, depending on which arm of the chromosome it is located.
EPO is the gene. Q21.13 is the locus of EPO
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
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)
AD: someone usually affected in each generation
AR: someone affected every other generation.
X-linked R: exhibited usually in males
X-linked D: twice as common in female families.
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)? (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
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? (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)
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
What is the epigenetic significance of X Chromosome Inactivation, and what is a barr body. Do barr bodies form when autosomal chromosomes are imprinted (as in for instance, AS and PWS?)
Barr body – female x chromosome that is rendered inactive
What is the general clinical characteristic of inherited mitochondrial disease?
Neuropathies and/or myopathies
What is the difference between penetrance, incomplete penetrance and variability?
Penetrence – the degree to which the phenotype is expressed
Incomplete penetrance – some genes are expressed to varying degrees, depending on
What is recurrence risk (RR) and how is it calculated (ans: multiply the penetrance by either 25% or 50% depending upon if the disease is AR or AD respectively)
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 BPs 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
Trisomy 21 is
Down’s Syndrome
Trisomy 18 is
Edward’s Syndrome
Trisomy 13 is
Patau Syndrome
Why aren’t there any autosomal Monosomies listed in the slides?
Incompatible with life
Turner’s (45X) characteristics
short stature, ovarian dysgenesis, and neurocognitive problems
Klinefelter’s (47XXY) characteristics
“hermaphrodite disorder” – hypogonadism, but ultimately normal appearing males
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? Know 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 Recipricol translocation of chromosomes 9 and 22 and is associated with CML (t9;22)
Can partial Monosomies occur? What would the karyotype of Down syndrome caused by a partial monosomy read? (slide 12 lecture 6)
Yes, partial monosomies can occur (due to translocations).
46,XX,-14,+t(14q;21q) or 46,XY,-
14,+(14q;21q)
What are knock-down studies? How do they work? What do they tell you about a gene? What the most effective modality for performing knock-down studies?
Experimental study in which genetic expression of a gene is reduced. This is most effectively done with iRNA.
This helps determine gene function.
Can iRNA be passed to subsequent generations?
No
What is iRNA?
Interference RNA - inhibits gene expression or translation by neutralizing targeted mRNA
Know the major reasons gene therapy did not work out well.
Infecting gene via virus into humans can be very challenging and potentially harmful
Were these mice pregnant or pregnant and in the 3rd trimester when sprayed with pesticides? (ans: NOOOO!) This suggests what about when epigenetic changes can take place?
suggests that epigenetic changes can occur at any point in the lifetime
In the Overkalix studies, it was found that nutritional influences and their subsequent epigenetic markers could be transmitted to future generations. 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. Also, are these the only times epigenetic effects can potentially be acquired by a person, and subsequently transmitted to future generations? (ans: NOOOOO!)
Epigenetic effects are imprinted into women when mother is in utero
Epigenetic effects are imprinted into males at any time
45. 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?
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
What is a ring chromosome, and what is its significance? How will it read on a karyotype? (what I am asking, is what do the letters coming before the chromosome numbers (r, t, i) each mean). For instance, what does this mean à t(9;22)(q34;q11)
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
Cri-du-chat results from what abnormality? Does the patient’s voice improve as they age?
Cry of Cat, caused by deletion on short arm of chromosome 5 leading to abnormal larynx development, though most develop normally after age 2
Angelman Syndrome
microdeletion of maternal 15, causing happy children who are ataxic and epileptic
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? (what I am asking, is what do the letters coming before the chromosome numbers (r, t, i) each mean). For instance, what does this mean à t(9;22)(q34;q11)
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
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?
Yes
