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Flashcards in midterm Deck (51):

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)



What is exon shuffling, and which part exon or intron remains as a section of the mRNA?

A molecular mechanism for the formation of new genes. It is a process through which two or more exons from different genes can be brought together ectopically, or the same exon can be duplicated, to create a new exon-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?



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


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). Usually due to gradual expansion of trinucleotide repeat polymorphisms within or near a coding gene.


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


Know the proper names (i.e. Alzheimer's, Wilsons, etc.) and basic characteristics for trisomy 21, 18, and 13

Trisomy 21 – Down’s syndrome: MC Autosomal trisomy, AVSD risk, ALL risk, decreased fertility, mental retardation, protruding large wrinkled tongue, flat nose and face, eye changes, short fifth finger, gap between 1st and second toes, GI defects.
Trisomy 18 – Edward’s syndrome: AVSD, PDA, Hand and foot malformations, Low set ears and micrognathia (small jaw)
Trisomy 13 – Patau Syndrome: Polydatyly, cleft palate, microphthalmia, microcephaly, cardiac and renal defects.
Both of these result in early death dt cardiac causes.


Why aren’t there any autosomal Monosomies listed in the slides?

Incompatible with life


Know the characteristics and Karyotype numbers for Turners syndrome, Klinefelter’s syndrome,  and XYY

Turner’s (45X) – Females, missing all or part of the X chromosome. Short stature, ovarian dysgenesis, and neurocognitive problems
Klinefelter’s (47XXY) – Intersex – 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 Reciprocal 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. 46XX or 46XY.


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


Know how Angelman Syndrome (AS) and Prader-Willi Syndrome (PWS) work, and their significance in the development of the field of epigenetics. (For instance, in PWS is it the maternal or paternal chromosome carrying the deletion? Then, which is imprinted)?  

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


 In which disease is the translocation described in question 39 most often associated with? (this is the same question asked a few questions above.)

t(9;22) is associated with the Philadelphia Chromosome and CML


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.


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


Did studies performed in mice demonstrate the cancer causing heritable changes in mice were not a result from a sequence change in the DNA itself?



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?



Know the major reasons gene therapy did not work out well

Therapeutic DNA must remain functional and cells with it must be long lived and stable.
Pt’s must undergo multiple rounds of gene therapy.
Immune response- mb severe and makes it difficult to repeat gene therapy dt immune cell memory.
Problems with vectors
Won’t work with multigene disorders
Most common disease are dt multiple genes and would be hard to Tx with gene therapy.

Infecting gene via virus into humans can be very challenging and potentially harmful. Eg severe immune response to carrier virus
Non Viral gene therapy can only be used with certain tissues and requires large amounts of DNA.


What is iRNA?

Interference RNA - inhibits gene expression or translation by neutralizing targeted mRNA.
RNAi is a process within living cells that moderates the activity of their genes. AKA co-suppression, post transcriptional gene silencing (PTGS) and quelling. Has an important role in defending cells against parasitic and viral nucleotide sequences


Can iRNA be passed to subsequent generations?

Yes- the reason that RNAi is such a big deal, means DNA is not the only form of inheritance.


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? (ans:  iR..)

Expression of one or more genes is reduced through genetic modification or a reagent such as short DNA or RNA.
Can help identify the components necessary for a particular cellular process or event such as cell division. Can be used to test the effect of mutated genes.
iRNA is the most effective modality for performing knock down studies


 Who was George price and what was his contribution to genetics?

A population geneticist, he contributed the Price equation and two other things to genetics. It determined how a gene or trait changes in frequency in the population over time.