2 - GENETICS Flashcards
what’s heredity?
the genetic passing of traits from a parent to progeny
how genes can be inherited and expressed by your children
define gene and allele and locus
gene: sequence of nucleotides that code for a specific product/trait
allele: variation in genes. e.g. different eye colours
locus: where the gene is on the chromosome
note that the chromosomes you inherit from mom and dad generally have the same genes but different alleles
for every gene in the human body, you carry 2 sets of alleles
differentiate between somatic cells and germ cells and gametes
somatic cells
- any non-reproductive cell
- diploid
- mutations that occur in somatic cells are not passed down to offsprings
germ cells
- diploids
- mutation that occurs in germ cells would be passed down to offsprings
- located in testes (males) and in ovaries (females)
- undergoes meiosis to form gametes – NOTE: germ cells are not sperm and egg cells but what produces sperm and egg cells via meiosis
gametes
- haploids
- sex cells (sperm and egg)
- combine to form diploid zygotes
- mutation that occurs in germ cells would be passed down to offsprings
what is a genotype?
the individual organism’s unique set of all the genes
the result of 2 copies of genetic information. one from the mother, one from the father. combination of genes from the parents
what is a phenotype?
physically observable characteristics
expression of the genotype we actually see
differentiate between homozygous, heterozygous, and hemizygous
homozygous: same allele type from mother and father
heterozygous: different allele type from mother and father
hemizygous: only a single copy of the gene instead of two – usually only happens with genes located on the sex chromosomes of males bc they have two different sex chromosomes with two completely different sets of genes OR if one copy of the gene somehow got deleted
what are the (3) laws of inheritance?
law of segregation: how individual gametes are formed. the gametes we produce only contain one allele after multiple (2) disjunctions during the anaphases.
law of independent assortment: how homologous chromosomes are separated independently from one another — no coordination –> genetically diverse outcomes. mendel confirmed this using his dihybrid crosses
law of dominance: the expression of dominant alleles
differentiate between monohybrid and dihybrid crosses
monohybrid: used to examine the inheritance of one particular set of alleles when two heterozygotes are crossed together
dihybrid: to examine inheritance and relationship between two sets of alleles when heterozygotes are crossed together – are the traits dependent or independent of each other?
what’s a test cross?
when the genotype of an organism expressing the dominant phenotype is unknown, the unknown organism is crossed with a homozygous recessive
organism to determine if the unknown is homozygous dominant or heterozygous dominant
what are the (7) patterns of inheritance?
mendelian inheritance: one allele dominates over the other
incomplete dominance: more than one dominant allele, and neither is completely dominant over the other. the phenotype will be a blend of the two alleles
codominance: both inherited dominant alleles are completely expressed, simultaneously.
multiple alleles: more than two possible alleles for a gene. e.g. eye colour
epistasis: one’s gene expression affects the phenotypic expression of another. e.g. having a gene that determines hair colour but also having a gene for baldness which affects the phenotypic expression of your hair
pleiotropy: a single gene affects multiple phenotypic traits - e.g. some diseases caused by lack of production of certain substances
polygenic inheritance: interaction of many genes shapes one phenotype e.g. height and skin colour
why are most sex-linked genes present on the x-chromosome?
because the y-chromosome is small, thus can only carry a few genes
what are sex-influenced genes?
sex-influenced genes don’t have to be located on a sex chromosome. sex-influenced genes are genes affected by the sex of the individual carrying that trait
i.e. being male or female can affect how the gene is expressed
what’s genomic imprinting?
allele expression (activation or deactivation) affected by which parent it came from
affects autosomal chromosomes
– not random
MOST GENES DO NOT UNDERGO GENOMIC IMPRINTING
what is penetrance in regards to phenotypic expression?
probability that an organism with a specific genotype will express the corresponding phenotype
complete penetrance = 100% of the people with the affected genotype will display the corresponding phenotype
incomplete penetrance = not all individuals with the affected genotype will display the corresponding phenotype
what is expressivity in regards to phenotypic expression?
describes the variation of a phenotype for a specific genotype - variety in the level of expression
what’s X-inactivation?
occurs in females
only one of the X-chromosomes needs to be expressed so methyl groups are added to the other X-chromosome, causing it to condense into a tiny structure called a barr body
process is random in determining which X-chromosome gets “turned off” – note that the chromosome is not completely shut off (THIS DOESN’T CAUSE TURNERS SYNDROME WHICH IS THE ABSENCE OF THE X-CHROMOSOME) females need both X-chromosomes for healthy function
—– this is why calico cats have multiple patches of fur
occurs during embryonic development
what’s the heterozygote advantage? explain the sickle cell example
for sickle cell
homo recessive - sickle cell disease & resistant to malaria
homo dominant - no sickle cell disease & susceptible to malaria
heterozygous - no sickle cell disease & resistant to malaria: these ppl have a mixture of normal and sickle blood cells. majority normal blood cells but enough sickle blood cells to be resistant to malaria
what are linked genes?
when two or more genes reside physically close to one another and are inherited together– due to crossing over
the closer the genes are to each other, the less likely they are to be separated
we can quantify how close genes are with another via recombination frequency, a percentage likelihood that two genes will be separated by crossing over – note that the highest recombination frequency for genes on the same chromosome is 50% due to the possibility of multiple swapping overs
consanguinity increases the possibility of what reoccurring in the pedigree chart?
likelihood of appearing recessive genetic conditions
what’s a point mutation? what are the (3) types of point mutations?
a mutation at the level of a single nucleotide
substitution
insertion
deletion
what’s a frame shift mutation?
caused by insertion and deletion mutations
shifts the template used (by the RNA transcript) to code for proteins – resulting in completely different amino acids being translated
differentiate between transition and transversion mutations
both are substitution mutations
transition: purine to purine; pyrimidine to pyrimidine
transversion: purine to pyrimidine, vice versa
differentiate between forward and backward mutations
forward: going from the (normal) wild type allele to a mutant allele
backward: going from a mutant allele back to the (normal) wild type allele
what’s non-disjunction?
when homologous chromosomes or sister chromatids do not separate during anaphase in mitosis/meiosis – resulting in too many genetic material in some cells and too little in others
if non-disjunction occurred at anaphase (mitosis), then the resulting cells would be labeled 2n+1 and 2n-1
if non-disjunction occurred at anaphase I or II (meiosis), then the resulting cells would be labeled n+1 (trisomy) and n-1 (monosomy)
what’s mosaicism?
occurs during embryonic development
when a multi-cellular organism has cells that are genetically different from one another - some cells will be abnormal some will be normal
can be caused from cells undergo mitotic non-disjunction during embryonic development
if from non-disjunction, fractions of body cells have extra or missing chromosomes
mosaicism can also result from point mutations and not just non-disjunction
what’s trisomy 21?
aka down syndrome
results from having an extra copy of the 21 chromosome due to non-disjunction
what’s aneuploidy?
occurrence of one or more extra or missing chromosomes in a cell or organism
– from non-disjunction
when it’s not 2n or n
what are chromosomal aberrations? what are the (5) types?
changes that occur to segments of DNA
- translocations
- duplications
- inversions
- substitutions
- deletions
describe the chromosomal aberration: translocations
when two different chromosomes swap segments
between non-homologous chromosomes
Robertsonian translocation: (one chromosome from a homologous pair becomes attached to another chromosome from a different pair).
For example, an extra chromosome 21 attached to chromosome 14 can cause
Down syndrome as well, due to the tripled 21 chromosome segment.
describe the chromosomal aberration: duplications
a segment of the chromosome gets duplicated – repeated segment
chromosome is longer than it initially was
describe the chromosomal aberration: inversions
a segment of the chromosome gets rearranged in the reverse orientation
chromosome has the same length it initially had
describe the chromosomal aberration: substitutions
only one chromosome segment gets moved to another chromosome
a one way donation, not a two way exchange like in translocation
describe the chromosomal aberration: deletions
a segment of the chromosome gets deleted
chromosome is shorter than it used to be
what’s a chromosomal breakage?
what comes before most chromosomal aberrations
a physical break forms in the chromosome that allows segments to detach
spontaneous or induced breakage of a chromosomal segment via mutagenic agents or X-rays
what are proto-oncogenes? what happens when a proto-oncogene becomes mutated?
they stimulate normal cell growth - tells the cell to multiply
after mutation: becomes hyperactive and starts overstimulating cell division– the now called oncogene can lead to cancer
e.g. RAS gene
what’s an oncogene?
a mutated proto-oncogene
it’s more hyperactive and overstimulates cell division in comparison to a regular proto-oncogene
can result in cancer
what are tumor supressing genes? what happens when a tumor supressing gene becomes mutated?
supresses excess cell growth - prevents cell from replicating too quickly/excessively
after mutation that decreases its function, cancer can potentially develop.
e.g. p53
how do viruses cause cancer?
viruses attach to cells and inject their genetic information
(in some viruses, the genetic info is used to make new copies of the virus which will eventually take over the cell and destroy it —– not cancer but….)
in other viruses, the genetic info gets integrated in the host genome. if the viral genome is inserted in the middle of genes that are critical for normal cell growth (like proto-oncogenes and tumor supressing genes) – then the function of the gene will be disrupted and cancer can develop
what are some commonly known autosomal dominant conditions? describe them
huntington’s disease: nervous system degeneration due to a protein accumulation in the brain
achondroplasia: causes dwarfism by limiting limb growth
hypercholesterolemia: excess cholesterol in the blood that progresses to heart disease
what are some commonly known autosomal recessive conditions? describe them
phenylketonuria (PKU): inability to produce the proper enzyme for the breakdown of the amino acid phenylalanine, leading to the degradation product, phenyl pyruvic acid accumulation which leads to health issues
cystic fibrosis: results in fluid buildup in the respiratory tract due to disrupted transport of salt and water across cell membranes
tay-sachs: defect in lysosomes so cells can’t break down lipids properly, affecting brain function
sickle-cell anemia: results in defective hemoglobin proteins that leads to misshaped blood cells that can’t carry oxygen properly
galactosemia: inability to break down the sugar galactose which can lead to organ damage
what are some commonly known sex-linked recessive conditions? describe them
hemophilia: abnormal blood clotting which leads to excess blood clotting from wounds
colour-blindness: inability to distinguish between red and green. primarily seen in males
duchenne’s muscular dystrophy: skeletal muscle mass is progressively lost
how can X-inactivation lead to one developing hemophilia?
a genetic disease that can result from
X-inactivation is hemophilia, a sex-linked recessive condition which results in an inability to form blood clots. XHXh is a normal carrier, but if XH (the normal, functional copy) is inactivated, then only Xh is expressed, leading to disease onset
what are some commonly known chromosomal (aneuploidy) disorders? describe them
down’s syndrome: 3 copies of chromosome 21. causes intellectual disability and health issues
turner’s syndrome: missing an x chromosome or part of it. they are sterile and have physical abnormalities
klinefelter’s syndrome: in males who have an extra x chromosome. they are sterile
cri du chat: individual is missing part of chromosome 5. results in intellectual disability
what does mitochondria with genetic defects result in?
reduced ATP production
what are maternal effect genes?
genes that when mutated in the mother, results in a mutant phenotype in the offspring (the mother has a normal phenotype)
maternal effect genes are like the genes that are responsible for producing critical materials for the eggs. if these gene products like egg proteins are defective in some way then the eggs will end up being defective as well.
what’s polyploidy?
when all chromosomes undergo meiotic nondisjunction and produce gametes with twice the number of chromosomes
is common in plants
how is colchicine a mutagenic agent?
colchicine functions by inhibiting spindle formation, which can cause polyploidy
how can a fetus be tested for genetic
disorders?
amniocentesis or chorionic villus sampling (CVS)
what does it mean when DNA replication is said to be a semi-conservative process?
each strand of DNA separately serves as a template, creating a new complimentary strand (for each)
so, every new DNA consists of one original strand and a new one
nucleotides on the same DNA strand are connected by what?
the DNA phosphodiester backbone
phosphodiester bonds between the sugar group of one nucleotide and the phosphate group of another
what holds together nucleotides on different strands of the DNA?
hydrogen bonds between the nucleobases
in what direction is DNA synthesized?
5’ to 3’
how are the two strands of DNA synthesized differently? why’s it done differently?
leading strand: top strand; synthesized continuously
lagging strand: synthesized as “okazaki fragments” that are later stitched together
the lagging strand is synthesized as fragments because it has to wait for the replication fork to unwound further before DNA polymerase can synthesize more fragments
describe the process of DNA replication
FORMATION OF REPLICATION FORK
- DNA separated into separate strands by an enzyme called DNA helicase, forming a y-shaped replication fork
- single-stranded binding proteins latch onto the separated strands to keep them separated and prevents them from coiling back together – this is done until the replication process is completed
- as we’re unwinding our DNA and separating the two strands, it can cause supercoiling and knots to build up in the DNA. to make sure the DNA structure remains nice and stable as we unwind, topoisomerase cuts and rejoins the DNA double helix just ahead of the replication fork, to prevent the knots and coils.
BINDING OF THE PRIMER
- primase lays out an RNA primer (a segment of RNA nucleotides) that allows the DNA polymerase to latch onto it
ELONGATION (LEADING AND LAGGING)
- in the leading strand, DNA polymerase III synthesizes DNA continuously in the 5’ to 3’ direction as the replication fork unzips
- at the same time, the lagging strand gets synthesized in fragments as it waits for the replication fork to unwind further (both strands are synthesized left to write and in the 5’ to 3’ direction at the same time!!)
- in the lagging strand as well, the DNA polymerase requires RNA primers to start synthesizing DNA. each okazaki fragment starts from a primer
TERMINATION
- DNA polymerase I removes the RNA primers and replaces them with DNA via a 5’ to 3’ exonuclease function
- DNA ligase fills in the gaps in the phosphodiester backbone between the fragments
- polymerase I and III also have a proofreading function that allows them to remove incorrect nucleotides and replace them
note that there are thousands of these replication bubbles open up, speeding up the process
what (3) enzymes are involved in the formation of the replication fork during DNA replication? describe what they do
DNA separated into separate strands by an enzyme called DNA helicase, forming a y-shaped replication fork
single-stranded binding proteins latch onto each of the separated strands to keep them separated and prevents them from coiling back together behind the helicase – this is done until the replication process is completed
as we’re unwinding our DNA and separating the two strands, it can cause supercoiling and knots to build up in the DNA. to make sure the DNA structure remains nice and stable as we unwind, topoisomerase cuts and rejoins the DNA double helix just ahead of the replication fork, to prevent the knots and coils.
what role does DNA polymerase III play in DNA replication?
synthesizes new DNA strands in the 5’ to 3’ direction
has a proofreading function where it can go back and remove incorrect nucleotides and replace them with the correct ones (a 3’ to 5’ exonuclease function)
mainly does replication
what role does DNA polymerase I play in DNA replication?
removes the RNA primers and replaces them with DNA nucleotides (a 5’ to 3’ exonuclease function) and can proofreads during this
has a proofreading function where it can go back and remove incorrect nucleotides and replace them with the correct ones (a 3’ to 5’ exonuclease function)
what does the central dogma of biology state?
the flow of information goes:
DNA -> can also replicate
- storage of genes
(transcription)
RNA
- intermediate for expression of genes
(translation)
proteins
- functional component of genes
note that DNA is simply a storage medium. to have our DNA become function, it must first be converted to an RNA intermediate and then, proteins. RNA can be said to serve as the bridge between the genotype and phenotype.
define gene expression
process by which DNA results in the synthesis of RNA and proteins, leading to expressible changes
gene expression = transcription + translation
note that DNA is simply a storage medium. to have our DNA become function, it must first be converted to an RNA intermediate and then, proteins. RNA can be said to serve as the bridge between the genotype and phenotype.
differentiate between RNA and DNA
RNA: ribonucleic acid
DNA: deoxyribonucleic acid
DNA contains deoxyribose sugar while RNA has ribose sugar. the key difference between these is that RNA has one more hydroxyl group
DNA is double stranded while RNA is single stranded
DNA has thymine while RNA has uracil as a nitrogenous base
where does the transcription of DNA take place?
in eukaryotes: nucleus
in prokaryotes: cytoplasm
what are the two strands of DNA called in transcription?
coding (aka sense) strand
template (aka anti-sense) strand: used by RNA polymerase to create mRNA
the mRNA will look very similar to the coding strand (but the mRNA will have uracil instead of thymine)
describe the process of transcription
RNA polymerase binds to a region in front of the region it’s going to transcribe, called the promoter (TATA box aka -10 element). the RNA polymerase is particularly attracted to the TATA box.
INTITATION
- transcription factors help the RNA polymerase bind to the promoter of the specific region we’re interested in expressing
- RNA polymerase unwinds the DNA
ELONGATION
- RNA polymerase continues to unwind the DNA as it synthesizes a strand of mRNA in the 5’ to 3’ direction using the template/anti-sense strand
TERMINATION
- RNA polymerase encounters a special sequence on the that causes the RNA polymerase to disassemble (usually a sequence of adenine nucleotides “AAAAAA”)
in what direction does transcription occur?
transcription is occurring in the 3’
to 5’ direction of the DNA template strand (but synthesis of the RNA strand is, as always, 5’ to 3’)
in the process of transcription, where does the RNA polymerase bind onto?
RNA polymerase binds to a region in front of the region it’s going to transcribe, called the promoter (TATA box aka -10 element). the RNA polymerase is particularly attracted to the TATA box.
the most common sequence of
nucleotides at the promoter region is
called the consensus sequence -
variations from it cause less tight RNA
polymerase binding, and therefore a
lower transcription rate
promoter region is upstream of the transcription start site
for transcription, how does your body decide which specific genes to express?
transcription factors
