Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
191 Cards in this Set
- Front
- Back
|
What are 4 characteristics of autosomal dominant pedigree patterns?
|
o Appears in every generation
o No gender differences o Fathers can transmit to sons o 50% of heterozygote will be affected o Limitations: small families |
|
|
What are 4 characteristics of autosomal recessive pedigree patterns?
|
o Does not appear in every generation
o No gender differences o Increased frequency in consanguinity o Can skip generations o 25% of 2 heterozygotes should be affected |
|
|
What are 3 characteristics of sex-linked dominant pedigree patterns?
|
o Does not skip generations
o No father-son transmission o Females more likely to show trait (2x as likely) |
|
|
What are 4 characteristics of sex-linked recessive pedigree patterns?
|
o Does not appear in every generation
o Males more likely to show trait (only 1 X) o Can skip generations o Females are often a carrier o No father-son transmission (man cannot give an x to a son) |
|
|
Define penetrance
|
o The degree to which a trait is expressed in a population
|
|
|
Define expressivity
|
o Different manifestations of the phenotype in an individual
• Could be genetic background • Could be environment |
|
|
What is an STS? What is it derived from?
|
A Sequence Tagged Site:
o Sequence is present once per haploid genome o Can be amplified by PCR o Defines a unique site |
|
|
What is an EST? What is it derived from?
|
EST is an expressed sequence tagged site
o Derived from cDNA |
|
|
How many different molecules of DNA do we have?
|
24. 22 autosomes, 2 sex chromosomes.
|
|
|
How may base pairs in the human genome?
|
3 billion
|
|
|
How much of the human genome is conserved sequences?
|
4.5%
|
|
|
How many genes do we have?
|
20-25,000
|
|
|
How many different molecules of DNA do we have?
|
24. 22 autosomes, 2 sex chromosomes.
|
|
|
How much of the human genome is comprised of transposons?
|
45%
|
|
|
o Centromeres
o Telomeres o Scaffolding attachment sites are examples of what? |
Extragenic sequences
|
|
|
hsp70 is an example of what?
What makes it interesting? |
A small gene. It has no introns.
|
|
|
Is gastrin small or large? Why is it interesting?
|
Small. It has a split exon arrangement.
|
|
|
Give an example of a modular gene, and descrive its structure.
|
Procollagen.
It is a trimeric helix. Every third helical structure connects with a glycine. |
|
|
Name a procollagen-mutation derived pathology and describe it in terms of severity.
|
Osteogenesis imperfecta. A small missense mutation is very severe, and dominant negative.
A major mutation is less severe. |
|
|
allelic heterogeneity involves
|
exons
|
|
|
locus heterogeneity involves
|
genes
|
|
|
many genes, same phenotype is known as
|
locus heterogeneity
|
|
|
many exons, same phenotype is known as
|
allelic heterogeneity
|
|
|
is osteogenesis imperfecta recessive or dominant?
|
Dominant. Looks recessive. Parents are often mosaics.
|
|
|
CFTR is an example of what? What makes it interesting?
|
A large gene. Lots of introns.
|
|
|
Cystic Fibrosis is a good example of a gene with what kind of heterogeneity?
|
Low locus heterogeneity
|
|
|
Loss-of-function mutations always follow a _________ inheritance pattern
|
recessive
|
|
|
Gain-of-function mutations always follow a _________ inheritance pattern
|
dominant
|
|
|
What does ∆F 508 mean ?
|
Change in phenylalanine at amino acid location 508.
|
|
|
What kinds of mutations could cause cystic fibrosis?
|
• Defective protein production (could be anything)
• Defective protein processing (post translational) • Defective regulation (maybe ATP) • Defective conduction (membrane spanning domains) • Defective splicing |
|
|
Dystrophin gene is on what chromosome? What kind of inheritance does it present with?
|
The X. X-linked recessive.
|
|
|
Who is muscular dystrophy seen mostly in?
|
Males. They only need one X.
|
|
|
What is the Dystrophin gene a good example of?
|
A large gene. 2.3 million base pairs.
Alternative splicing patterns. 5' end has 2 promoters, 3' has 1. |
|
|
What does acrocentric mean?
|
Short P arm
|
|
|
which are the acrocentric genes?
|
13, 14, 15, 21, 22
|
|
|
What do the acrocentric genes have in common?
|
They all code for ribosomal RNA
|
|
|
Where do the acrocentric genes congregate?
|
Together. In the nucleolus.
|
|
|
How do the genes for ribosomal RNA maintain such stability?
|
Non-allelic recombination.
|
|
|
Commonly utilized way of looking at inheritance pattern
|
Pedigrees
|
|
|
Hemizygous refers to
|
Males
|
|
|
Is dominant/recessive more appropriate at the organismic or cellular level?
|
Organismic
|
|
|
When did the human genome project begin? How long did it take?
|
1990. Took 13 years.
|
|
|
What were 3 goals of the Human Genome Project?
|
Sequence Genome
Build databases Come up with new ways to analyze it |
|
|
What were the first three genomes sequenced?
|
E. Coli, Drosophila, Mouse
|
|
|
What industry did the HGP start?
|
Biotechnology
|
|
|
What does ELSI mean?
|
Ethical, Legal and Social concerns
|
|
|
What were three stages in the genome project?
|
Genetic map (recombination frequencies)
Physical map (Sequence Tagged Sites) non-repetitive DNA Identify polymorphisms (SNPs, RFLPs) |
|
|
On average, how many differences in nucleotides between people do we see?
|
500-1000 bp
|
|
|
What is an antimorph?
|
A mutant expressing some agent that antagonizes a normal gene product.
Poison product. |
|
|
Loss-of-function generally shows a __________ inheritance pattern
|
Recessive
|
|
|
Gain-of-function generally shows a __________ inheritance pattern
|
Dominant
|
|
|
OI has _______ ________ heterogeneity and _______ _______ heterogeneity
|
high allelic, high locus
|
|
|
Examples of large genes are
|
CFTR (Cystic Fibrosis Transmembrane Regulator)
Dystrophin Gene |
|
|
What domain of CFTR is completely encoded by a single exon?
|
R-domain (Regulatory)
|
|
|
What does a highly-salty sweat suggest?
|
Improper chloride ion transportation in CF ion channel.
|
|
|
Is CF a high or low allelic heterogeneity disease?
|
Low. But it has a high one across populations.
|
|
|
How long does the Dystrophin gene take to transcribe?
|
16-24 hours
|
|
|
What pattern does Muscular Dystrophy follow?
|
X-linked recessive
|
|
|
How many exons does the dystrophin gene have?
|
79
|
|
|
How many promoters does the dystrophin gene have?
|
3
|
|
|
What does the product of dystrophin gene do?
|
mediates growth and stability of muscles
|
|
|
How many base pairs in the dystrophin gene?
|
2.3 million
|
|
|
Deletions and duplications are associated with
|
Frameshift mutations
|
|
|
Gene families are clustered or distributed?
|
Both
|
|
|
Why would we need multiple copies of a gene? (3 reasons)
|
Redundancy (backup)
A large amount is needed It can acquire novel characteristics |
|
|
Why are ribosomal RNA and histone genes so widely represented?
|
A large amount of gene product is needed at certain times.
|
|
|
What is a pseudogene?
|
It is a non-functional member of a gene family. They may be remnants of mutated genes.
|
|
|
Why are ribosomal RNA genes considered to be a family?
|
They are all on acrocentric chromosome.
|
|
|
What chromosomes code the ribosomal RNA genes
|
21, 22, 13, 14, 15
|
|
|
Acrocentric centromeres have the centromere ___________
|
close to one end
|
|
|
Metacentric centromeres have the centromere ___________
|
in the middle
|
|
|
Where are ribosomal RNA genes located in the nucleus?
|
They are collected in the nucleolus, which makes ribosomal RNA.
|
|
|
How do ribosomal RNAs maintain such similarity?
|
non-allelic recombination
|
|
|
How does the y chromosome stay so homogeneous?
|
Non-allelic recombination. Like Ribosomal RNA.
|
|
|
Are the photopigments all alike?
|
No.
|
|
|
Normal color vision is called _______ vision
|
Trichromatic vision
|
|
|
Red and green opsins are coded for on the _________ chromosome
|
X
|
|
|
The most common color blindness is called ____________ color blindness
|
dichromatic
|
|
|
Deuteranopia means
|
Can't see green.
|
|
|
Protonopia means
|
Can't see red.
|
|
|
Red-green genes have __________
|
an extra exon.
|
|
|
Every human has how many red and green genes?
|
1 and at least 1.
|
|
|
The difference between red and green lies in
|
exon 5.
|
|
|
What happens when we have internal duplications in chromosomes?
|
Ectopic pairing, unequal crossing over
|
|
|
Red-green fusions result in
|
anomalous color detection, but not color-blindness
|
|
|
Old-world monkeys have how many color genes? New world?
|
3, 2.
|
|
|
What are 2 main categories of extragenic DNA?
|
Unique and highly-repetitive
|
|
|
What are some examples of tandem or clustered repeat DNA
|
Satellite, microsattelite
|
|
|
What are some extragenic DNA examples that are unique?
|
Gene fragments, pseudogenes
|
|
|
Where is satellite DNA found?
|
Centromeres
|
|
|
What is the size of repeat of satellite DNA
|
5-171 bp
|
|
|
Where is minisatellite DNA found?
|
At telomeres
|
|
|
What is the size of repeat of minisatellite DNA
|
9-64 bp
|
|
|
What is the size of repeat of microsatellite DNA?
|
12 bp.
|
|
|
Where is microsatellite DNA found?
|
All over.
|
|
|
How did we used to study DNA in the past?
|
Biochemical methods. Density tests (buoyant). This is where the moniker "satellite" comes from.
|
|
|
What is a VNTR?
|
Variable Number of Tandem Repeats. This is often used in DNA fingerprinting.
|
|
|
What is an SSR or STR?
|
Short Simple Repeat or Short Tandem Repeat. Name for microsatellites.
|
|
|
What is the difference between a SNP and RFLP?
|
More opportunities for polymorphisms in RFLPs.
|
|
|
Most transposons are
|
Retrotransposons (transpose via RNA)
|
|
|
What sort of transposons are ALUs?
|
Non-autonomous. SINES. Short Interspersed Elements.
|
|
|
What sort of transposons are LINES?
|
Viral. Long Interspersed Elements.
|
|
|
How does a retrovirus work?
|
RNA copies itself into DNA (Reverse transcription) that integrates into DNA genome.
|
|
|
SSR stands for
|
Short Simple Repeats
|
|
|
STR stands for
|
Short Tandem Repeats
|
|
|
SSRs and STRs are examples of
|
Microsatellites
|
|
|
LINES ________________________
and SINES ________________________ |
Encode Reverse Transcriptase
Do not encode Reverse Transcriptase (ALUs) |
|
|
LINES stands for
|
Long INterspersed Elements
|
|
|
SINES stands for
|
Short INterspersed Elements
|
|
|
A retroviruslike element is...
|
A transposable element that uses reverse transcriptase to transpose, through an RNA intermediate.
|
|
|
Transposons are able to gain easier access to promoter elements, why?
|
Because they are more accessible to modification.
|
|
|
What are some features of the retroviral family of transposons?
Give an example: |
Long terminal repeats
Reverse transcriptase This is an RNA-dependent DNA polymerase These are non-specific (location-wise) ::: THE1 family |
|
|
Where does a poly-a tail manifest?
|
messenger RNA, LINES
|
|
|
Non-viral family has no
|
Reverse transcriptase
|
|
|
SINES have no
|
Reverse transcriptase
|
|
|
LINES have reverse transcriptase that acts in __________
|
Trans
|
|
|
_______ and ________ have a __________ tail
|
LINES and SINES have Poly-A tails
|
|
|
The name Alu comes from...
|
A restriction enzyme
|
|
|
The most common sequence in the human genome is the ______, with about _____________ copies.
|
Alu, 1,000,000
|
|
|
The Alu sequence is believed to be originated in
|
7SL RNA.
|
|
|
The Alu looks like an
|
Imperfect dimer, missing b and d on left.
|
|
|
FRAMs and FLAMs refer to
|
Free Left and Right Alu Monomer
|
|
|
Where does RT come from for Alus?
|
Probably LINES.
|
|
|
How does neurofibromatosis?
|
An inserted Alu element in an intron screws up splicing.
|
|
|
DNA Methylation, most basically, is
|
a form of transcriptional regulation
|
|
|
What kind of DNA is more heavily methylated?
|
Pericentromeric
|
|
|
Why might methylation be useful in terms of retrovirii?
|
It could limit the expression of the retrovirus.
|
|
|
Are most genes regulated by methylation?
|
No.
|
|
|
Most repetitive DNA is associated with
|
Methylation
|
|
|
How many genes are imprinted? What is a mechanism for repression?
|
Fewer than 100. Methylation.
|
|
|
Methylation is significant in what 2 areas?
|
X-inactivation, imprinting.
|
|
|
Most methylation is at what carbon?
|
The 5th.
|
|
|
What is the process (chemical) of methylation?
|
SAM to SAH (S-adenosyl-methionine to S-adenosyl homocysteine)
via the 5th carbon of cytosine. Cytosine to 5-methylcytosine. |
|
|
All methylcytosines that are present are in
|
CpG dinucleotides, with a guanine at 3' position.
|
|
|
What are enzymes involved in methylation?
|
DNMT1 (DNA Methyltransferase 1)
DNMT 3a, 3b (DNA Methyltransferase 3a, 3b) |
|
|
DNMT1 (DNA Methyltransferase 1) is involved in
|
Maintenance methylation of hemimethylated DNA
|
|
|
DNMT3a, 3b (DNA Methyltransferase 3a, 3b) is involved in
|
De novo methylation
|
|
|
CpGs are often found in
|
Islands
|
|
|
CpGs are ______________ than we would expect
|
less frequently found
|
|
|
What is a transition? In terms of nucleotides?
What is a transversion? |
Purine to purine, pyrimidine to pyrimidine.
The opposite. |
|
|
What happens in normal cytosine deamination?
|
Uracil DNA glycosylase fixes it.
|
|
|
What happens in methylated cytosine deamination?
|
It gets converted to Thymine.
|
|
|
CpG regions are clustered in
|
5' regions
|
|
|
What is the activator exclusion model, and 2 subtypes?
|
Methylation inhibits binding of transcription factors.
This can be done directly or indirectly. |
|
|
What is the intermediate in indirect activator exclusion?
|
Methyl-C binding proteins
|
|
|
MeCP and MBD stand for
|
MethylC binding Proteins
Methyl binding Domain Proteins |
|
|
What are the core histones?
|
H2a, 2b, 3, 4.
|
|
|
What is MeCP2?
|
It is a Methyl Binding Protein
|
|
|
What are the 2 steps in Methylation-associated chromatin modification?
|
1. DNMTs (MeCP2) recruit HDAc; repression
2. MBDs draw HDAc Or, just MECP2, HDAc, MBDP, HDAc |
|
|
Epigenetic code is heritable: T/F
|
True
|
|
|
Epigentic modification is like _______ in text.
|
formatting
|
|
|
ICF syndrome is due to
|
A mutation in DNAMT3b
|
|
|
In ICF Syndrome, which chromosomes are not affected?
|
1, 9, 16
|
|
|
What is a HAT?
|
Histone Acetyl Tranferase
|
|
|
What is Rett’s Syndrome?
|
It is X-linked, usually fatal in males
|
|
|
How is Cancer regulated by methylation?
|
Hypermethylation removes regulation expression
|
|
|
What is an HDAc?
|
Histone De Acetylase
|
|
|
How did the sex chromosomes evolve?
|
From autosomes
|
|
|
What does the Y do?
|
It determines maleness
|
|
|
Klinefelters is
|
Male. XXY
|
|
|
Turners is
|
Female. XO
|
|
|
Do the X and Y pair?
|
Yes. During Meiosis 1.
|
|
|
What is the PAR?
|
The Pseudoautosomal region
|
|
|
Where are the PARs?
|
Telomeric regions of p and q
|
|
|
What is the big male gene?
|
SRY
|
|
|
What does SRY encode?
|
TDF
|
|
|
What is TDF?
|
Testis Determining Factor
|
|
|
Are XXX or XO normal?
|
No. Haploinsufficiency, PAR genes.
|
|
|
When is significant about Y-chromosome appearance?
|
To detach from environmental cues
|
|
|
What are the ancestral X regions called?
|
X-conserved
|
|
|
What was surprising in the Y-chromosome?
|
The ampliconic region; much like the rDNA regions.
|
|
|
What is the Xi sometimes called?
|
Barr body
|
|
|
What is a good example of an x-linked disease affected by X-inactivation?
|
Duchenne Muscular Dystrophy
|
|
|
Name 2 characteristics of an inactive X
|
Replicates later in S-phase
Extensively methylated |
|
|
What is the XIC?
Function? |
X inactivation center;
Initiation and propogation |
|
|
What is XIST?
Function? |
X Inactive Specific Transcript
Start and Spread |
|
|
What is the XCE?
Function? |
X Controlling Element
-Choice |
|
|
What is TSIX
|
Regulates XIST in an antisense fashion
|
|
|
What is XCITE?
|
X-Intergenic Transcription Elements
|
|
|
Does choice require transient pairing? How do we know?
|
Yes. If we ablate the XIC, pairing does not happen, no inactivation.
|
|
|
Unequal X-inactivation can be due to
|
Tissue selection
|
|
|
What are proposed as way-stations for XIST RNA
|
LINES. Twice as abundant on X-chromosome.
|
|
|
What does XIST RNA recruit?
|
Histone Methyltransferase, Histone Deacetylase
|
|
|
What is the 2-factor model for TSIX?
|
X+Autosome factor = Active
|
|
|
Geonomic imprinting is only found in mammals? T/F
|
True
|
|
|
Define genomic imprinting
|
The differential activation of an allele depending upon the parent from which it is inherited
|
|
|
How may traits are uni-allelic?
|
Less than 100
|
|
|
When is the imprint made?
|
During gametogenesis
|
|
|
Is imprinting reversible?
|
Yes. It is usually sex-specific.
|
|
|
Name 2 diseases based in imprinting
|
Prader-Willi, Angelman’s syndrome
|
|
|
How is Prader Willi imprinted?
Angelmans? |
Mom
Dad |
