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