exam 1 Flashcards
genome
entire set of DNA instructions found in a cell
in a virus, cell, or organelle
What carries a human genome?
a. 23 chromosomes
b. 23 chromosomes + mtDNA
c. 46 chromosomes
d. 46 chromosomes + mtDNA
**a. 23 chromosomes ** or b. 23 chromosomes + mtDNA
context is important
how many genomes are there in a virus
1 genome
can be RNA or DNA
how many genomes are there in a bacteria cell
1 genome
how many genomes are in an animal cell
2 genomes:
1. nucleus (nDNA)
2. mitochondria (mtDNA)
how many genomes are there in a plant cell
3 genomes:
1. nucleus (nDNA)
2. mitochondria (mtDNA)
3. chloroplast (cpCNA)
what is the size of eukaryotic genomes
10Mb → 100,000Mb
contained in organelles
characteristics of chromosomes in eukaryotic nuclei
- multiple linear chromosomes
- multiple copies of each chromosome
characteristics of mitochondrial genomes
12kb–2400kb
- circular DNA
characteristics of chloroplast genomes
120kb–170kb
- circular DNA
viruses
infectious particles comprised of a genome surounded by a protein coat
viral genomes
- 2000 to 1 million bp of RNA or DNA
- linear or circular
- single stranded, double stranded, or segmented
- 1 genome (RNA or DNA)
viral genomes frequently invade the genomes of other organisms
prokaryotic genomes
1 chromosome (DNA)
* 0.6-12Mb
* circular
* found in the nucleoid
* haploid
may have plasmids
* small circles of DNA
* 1-200kbp
* autonomously replicating
* not present in all bacteria
methods for visualizing chromosomes
- Geimsa dye staining
- microscopy
- sorting
karyotype
refers to an individual’s complete set of chromosomes (46XX, 46XY)
* also refers to the image of a person’s organized chromosomes
* created by cytogeneticists
cytogeneticists
detect and interpret chromosomal abnormalities
1. cells are collected
2. cells are grown for a little while to initiate DNA replication
3. chromosomes are analyzed
types of reproductive genetic testing
1. prenatal testing
* amniocentesis (16 weeks)
* chorionic villi sampling (11 weeks)
* maternal blood testing (9 weeks)
2. preimplantation genetic diagnosis (PGD)
note: PGD can only be used with in-vitro fertilization
4 ways of classifying chromosomes based on size and position of centromere
- metacentric
- submetacentric
- acrocentric
- telocentric
metacentric chromosome
centromere in the middle
* forms two equal arms
submetacentric chromosome
centromere placed near to one end
* results in one shorter and one long arm
acrocentric chromosome
centromere placed closed to one end
* forms one extreme short and one extreme long arm
telocentric chromosome
terminally placed centromere
cohesins
holds sister chromatids together during mitosis
chromosome number (N)
this is the number of unique chromosomes in a “set”
ploidy
number of complete sets of chromosomes
what is the best way to count the number of total chromosomes
count the number of centromeres
haploid chromosome number (N) and ploidy are…
specific to a species
* e.g. Homo sapiens N=23, 2N=46
c-value
amount of nuclear DNA in a gamete (haploid)
- this is irrespective of ploidy
note: organismal complexity is not correlated with N, ploidy, or # genes
genome packaging in prokaryotes is ____ organized than in eukaryotes
less
C-value paradox
organismal complexity is not correlated with N, ploidy, or # of genes
nucleoid
region that contains condensed DNA/protein complexes
- attaches to inner membrane
note: this is characteristic of prokaryotes
NAPs
nucleoid-associated proteins
- these bind to repetitive sequences to form loops of supercoiled DNA
- ~10,000 bp/loop
microdomains/loop domains
help to condense bacterial chromosomes
how does a bacterial genome fit inside the cell?
supercoiling helps pack DNA into smaller spaces
what is supercoiling facilitated by
enzymes
(i.e. topoisomerases)
topoisomerases
enzymes that overwind and underwind dsDNA
positive supercoiling
overwinds DNA
negative supercoiling
underwinds DNA
drugs that inhibit topoisomerases are one type of…
chemotherapeutic agent
eukaryotic genome packaging is
organized
nucleosome
refers to a single histone/DNA complex
- the fundamental subunit of chromatin
eukaryotic histones in a nucleosome:
- composed of: (1) a core histone octomer & (2) a linker histone
p-arm
petit
- this is the short arm
q-arm
queue
- this is the long arm
p telomere called…
ptel
- this is on the short arm
q telomere called…
qtel
- this is on the long arm
do 2 different individuals from the same species have the same banding patterns on their chromosomes?
yes
FiSH
fluorescent in situ hybridization
- used to visualize specific regions of a genome (typically when abnormalities are suspected)
- a DNA or RNA probe complementary to a specific region of the genome is hybridized to chromosomes
- can also use lots of probes that are labeled with different colors to “paint” chromosomes
FISH can identify differences in…
base-pair order
how do chromosomes occupy the nucleus
within specific territories
- likely allows for specific interactions between different chromosomes
T/F: regions of genomes will condense and decondense at different times
TRUE: genomes are dynamic
- sometimes our cells need to “see” the DNA in an uncondensed form (for DNA replication, gene expression, etc.)
isolated chromosomes contain:
- DNA
- proteins
- RNAs
- lipids
- polysaccharides
when interpreting chromosomal data, what to look for:
- # of each chromosme
- total # of chromosomes
- centromere position
- chromosome length
- chromosome shape (linear)
- banding patterns
What % of the human genome is composed of protein coding genes?
the human genome is 3 billion base pairs long
2%
the amount of non-coding DNA varies between species
non-coding DNA contains
- introns
- transposable elements
- repetitive sequences
- stuff we still don’t understand (unique sequences)
introns
parts of genes that are transcribed into mRNAs, and then removed before translation
what can create different proteins
alternative splicing
- this might explain why humans only have 20% more genes than a single celled plasmodium
introns position
members of the same species: tend to have the same introns in the same positions
members of different species: can gain or lose introns, but will maintain ancestral positons of introns more frequently than expected
- suggests functionality
transposable elements (TEs)
self-replicating, mobile DNA sequences
- “jumping genes”
- classified as “selfish” genetic elements or “genomic parasites”
purpose of transposable elements
not “junk”, might provide genetic variation that is favored during evolution
- can also contribute to regulatory changes (TE upstream of ISL1 alters gene expression)
- novel proteins through changes in intron splicing ?????
repetitive sequences
can be:
1. short and sequential
- can consist of (1) simple repeats (SSRs), (2) simple tandem repeats (STRs), and (3) microsatellites
2. long and segmented
i.e. intrachromosomal vs. interchromosomal
test cross
cross an unknown to an individual with a known, recessive genotype
- offspring will have predictive phenotypic ratios for the possible unknown genotypes
what occurs to TEs that copy and insert themselves into important genes
they should be selected against over evolutionary time
who established “true breeding” pea lines
Gregor Mendel
- created peas that were homozygous
- showed that F1 and F2 offspring had predictable ratios of phenotypes
what occurs if a TE is copied and inserted into a non-coding sequence
it will be maintained
- the larger the non-coding sequence space, the more likely a TE will land in an unimportant region
- this would make the non-coding sequences longer and allow for the expansion of more TEs
Mendel’s discoveries
there are 6 of them
- there are “hereditary determinants of particulate nature” (genes)
- genes come in pairs
- alternate phenotypes of a single character are determined by different forms of these genes (dominant/recessive alleles) (Law of Dominance)
- gametes contain one member of each gene pair (ploidy)
- innheritance of alleles was random/random fertilization (Law of Segregation)
- genes controlling different traits are inherited independently (Law of Independent Assortment)
what are Mendel’s Laws of Heredity
there are 3 of them
- Law of Dominance
- Law of Segregation
- Law of Independent Assortment
Law of Dominance
some alleles are dominant, others are recessive, a heterozygous individual will display the dominant form
- this is one of Mendel’s laws of heredity
Law of Segregation
only 1 allele is carried in a gamete
- this is one of Mendel’s laws of heredity
Law of Independent Assortment
genes of different traits segregate independently to the gametes
- this is one of Mendel’s laws of heredity
what are the steps of meiosis
- interphase
- meiosis I
- prophase I
- metaphase I
- anaphase I
- telophase I - meiosis II
- prophase II
- metaphase II
- anaphase II
- telophase II
what steps can prophase I (meiosis) be further broken down to
- leptotene
- zygotene
- pachytene
- diplotene
- diakinesis
interphase
DNA replicates
prophase I
homologous chromosomes find each other and recombine
metaphase I
chromosomes align on metaphase plate
anaphase I
chromosomes move to opposite poles
telophase I
cell division
prophase II
chromosome structures condense, no crossing over
metaphase II
chromosomes align to a central plane
anaphase II
chromosomes move to opposite poles
telophase II
cell division
monohybrid cross
when both parents are heterozygous at 1 locus
- e.g. Aa x Aa
dihybrid cross
when both parents are heterozygous at 2 loci
- e.g. LlAa x LlAa
one meiotic event describes…
the entire process of going from one diploid germline cell to 4 haploid gametes
consider LlAa where both loci are on separate chromosomes
- if there is no recombination, how many meiotic events woul it take to generate all possible genotypes of gametes?
check notes and fill in
frequency of recombination depends on…
how close the loci is to the centromere
- recombination doesn’t happen at the centromere
predicted genotype ratios for mono and dihybrid crosses will…
always be the same
predicted phenotype ratios will depend on…
the relationship of the alleles
number of unique gametes (ignoring recombination) =
2N
heterochromatin
these regions are typically full of repetitive sequences
- this may aid in compacting genome
segmental duplications
1kb-400kb repeated sequences
what explains the highest % (~44%) of our genome?
transposable elements (TEs)
how much of a human genome is variable between individuals?
0.1%
- variation is randomly distributed across the genome
- not all variation is in coding sequences
T/F: genetic variation is primarily in coding regions
FALSE
- variation is randomly distributed across the genome
- not all variation is found in the coding sequences
types of genetic variation between individuals
- single nucleotide polymorphisms (SNPs)
- copy number variants (CNVs)
- trinucleotide repeats TNRs
single nucleotide polymorphisms (SNPs)
this is a variation at a single position in a DNA sequence among individuals
- between any 2 humans: ~ 1 SNP every 1000 bp
- 3-5 million SNPs/genome
copy number variants (CNVs)
when the number of copies of a particular gene varies from one individual to the next
- between any 2 humans: ~1500CNVs
- avg. size of CNV=~20k bp
examples:
trinucleotide repeats (TNRs): TAGTAGTAGTAGTAG
T/F: the majority of SNPs/CNVs lead to phenotypic differences
FALSE
what region of the genome do SNPs and CNVs occur in
coding and non-coding regions
- they both can cause changes in phenotype but most of the time they have no phenotypic effect
trinucleotide repeats
3 nucleotides consecutively repeated within a region of DNA
- this is a type of copy number variant (CNV)
when can TNRs lead to disease
- when they occur within important genes
(e.g. Huntington’s Disease) - when they occur at structurally important regions of a chromosome
(e.g. Fragile X syndrome)
note: TNRs in non-coding regions that haave o phenotypic effecs are ofen used for identity analysis
between which of the following do you expect to differ between individuals of the same species?
1. number of chromosomes
2. chromosome sizes
3. types and positions of introns
4. numbers of genes
5. types of genes
6. alleles
7. CNVs
8. SNPs
FILL IN W NOTES
which of the following do you expect to differ between individuals of different species?
1. number of chromosomes
2. chromosome sizes
3. types and positions of introns
4. numbers of genes
5. types of genes
6. alleles
7. CNVs
8. SNPs
FILL IN W NOTES
dominance/recessive relationships
when one copy of an allele overrules phenotypes conferred by a different allele
- heterozygotes and homozygotes for completely dominant alleles show the same phenotype
codominant relationships
heterozygotes for codominant alleles show both phenotypes
- e.g. orange and black alleles in cats- both also happen to be X-linked
incomplete dominance
heterozygotes for incomplete dominant traits show a phenotype that is somewhere in between both homozygotes
- e.g. piebald spotting in cats
which steps of meiosis generates genetic diversity?
- interphase
- prophase I
- metaphase I
- metaphase II
genetic dominance/allelic relationships only compare the relationship between one allele in relationship to other alleles where
at the same locus
modifier genes/alleles
alter the phenotypic effects of other genes
- e.g. modifier genes affect the hair length
main/major effect vs. minor effect loci
major effect loci has more of an effect on allele than minor effect loci
does environment play a role in phenotypic expression
yes
if event “A” and “B” are independent events…
AND = multiply
- mutiply independent probabities
- e.g. AaBb X AaBb, P(A_B_)= P(A_)*P(B)
if event “A” and “B” are dependent events
OR = add
- add dependent probabilities
- e.g. P(A_) or P(B_) = P(A_) + P(B_)
pleiotropy
the production by a single gene of two or more apparently unrelated effects
pleiotriopic alleles lead to many different phenotypes (hair color, deaf, eye color)
- 1 gene, many phenotypes
epistatic alleles
masks the effects of alleles at other genes
- if one allele prevents you from being able to predict the genotype at annother locus, the you have epistasis
binomial expansion for phenotypic probability
must define your variables
- e.g. a = probability of having a child with normal RBC, b = probability of having sickled RBC
- use Pascal’s triangle
binomial equation for 3 children
(a+b)^3 = a^3+3a^2b+3ab^2+b^3
binomial equation for 5 childre
(a+b)^5 = a^5+5a^4b+10a^3b^2+10a^2b^3+5ab^4+b^5
are males or females more likely to show phenotypes of sex-linked traits
males
sex
refers to the aatomy of an individual’s reproductive system and secodnary sex characteristics
gender
refers to social roles or internal awareness based on the sex of a person
how do sex chromosomes pair up during meiosis
using pseudoautosomal regions
1. primary pseudoautosomal region found on the short arm
2. secondary pasudosomal region found on the long arm
found on both X and Y chromosome
what should you do to test for sex linkage
perform a reciprocal cross
- a pair of crosses between the male of one strain and the female of another, and vice versa
- if sex linked, phenotypic ratios will be different in a reciprocal cross
how to perform a chi squared (x^2) goodness of fit test
- presnent the assumed genotypes of cross you are testig
- present the observed and expected data in a table
- state an explicit null hypothesis pertaining to defined cross
- calculate the X^2 statistic
- state the degrees of freedom (and show its calculation)
- determine the X^2crit for the appropriate alpha value (P value) to test for significance
- compare the X^2crit to your X^2 value, and state whether or not the H0 is rejected
- state the overall conclusion
William Warrick Cardozo showed that
- sickle cell anemia
- is more common among people with African ancestry
- not all people with sickled red blood cells have anemia
- not all sickle cell anemia cases are fatal
if a trait is rare, it is safe to assume that…
(pedigrees)
non-blood relatives are not carriers
- however if you know mode of inheritance, can deduce that someone entering a pedigree must be a carrier
dominant traits
- the first person in a pedigree to show the trait is most likely heterozygous
autosomal dominant traits tend to
- appear equally in males and females
- doesn’t skip generations
- affected children have an affected parent
- unaffected people do not transmit the trait
autosomal recessive traits tend to
- appear equally in males and females
- skip generations
- more to appear among progeny of related parents
X-linked dominant traits tend to
- does not skip generations
- affected males pass trait to all daughters and no sons
- affected heterozygous females pass trait to half of sons and half of daughters
X-linked recessive traits tend to
- affected males produce carrier daughters
- no sons of affected males are affected
- males more likely to be affected than females
- half of the sons from an unaffected carrier will be affected
Y-linked traits tend to
- traits appear only in males
- all sons of affected males will be affected
mitochondrial (mtDNA) traits tend to
- affected females pass the trait to all children
- affected males never pass down the trait
- mtDNA traits often show incomplete penetrance
*
incomplete penetrance
when not every individual that must be a particular genotype shows the expected phenotype
heteroplasmy
the coexistence of multiple mtDNA variants in a single cell or among cells within an individual
- mtDNA heteroplasmy is common in humans
- cells have many copies of mtDNA
does organelle inheritance follow Mendelian ratios?
NO
- random segregation of mtDNA during meiosis annd mitosis leads to unequal inheritance of mtDNAs
what happens with an mtDNA variant that contains a disease-causing allele
if it reaches a certain threshold, disease symptoms arise
what are the 6 modes of inheritance
- autosomal dominannt
- autosomal recessive
- X-linked dominant
- X-linked recessive
- Y-linked
- mitochondrial
rare vs. common traits
autosomal recessive traits can look like autosomal dominant when alleles are common in the population
- if an allele is common, we can’t assume that people entering the pedigrees are NOT carriers
what are questions you may need to know to label a pedigree
- what is the mode of inheritance of the trait?
- what are the genotypes (or possible genotypes) of the parents?
- what are the possible crosses that could produce an affected child?
- what are the individual probabilities of each cross?
- what are the total probabilities?
conditional probability
p(A|B) is the probability of event A occurring, given that event B occurs
law of total probability
look at notes
