Principles of Genetic Inheritance Flashcards
Gene
segments of DNA on a chromosome
What is a chromatid?
One of two identical copies of a chromosome
two chromatids are connected at the _____ to create a _______
Two chromatids are connected at the centromere to create a chromosome
Human somatic cells
diploid (2n)
23 pairs of chromosomes= 46 chromosomes
one from mom and one from dad
Gametes
haploid
23 chromosomes
Autosomes
chromosomes that are not sex chromosomes
What is the position of a metacentric centromere?
the q and p arms are both of equal lengeth
What is the position of a submetcentric centromere
P arm is smaller than q arm
What is the position of a acrocentric centromere
P arm is v small (almost cant see it), making the chromosome at the end. thus, little genetic info is there
homologous chromosomes
1 pair of chromosomes (1 from mom and 1 from dad)
Homologous chromosomes have variations of the same gene in the same location
Banding in a chromosome
- ARMS: p and q
- Arms are then divided into TWO REGIONS (1,2)
- Band
- Subband
Name the location of the band
17q11.2
17th chromosome Arm= q Region= 1 Band=1 Subband=2
What are used to indicate bands?
Staining techniques
Karyotype
the entire set of a patients chromosomes
How are chromosomes in a karyotype presented?
- a single condensed chromosome
2. Duplicated chromosome
What is Lyonization
Lyonization is X-inactivation. Females inherit two X chromosomes. Thus, one of them is RANDOMLY condensed into a Barr body because too much gene expression is mad.
Can Barr bodies be passed down to offspring?
Yes, Barr bodies can be passed down to offspring.
Why do females not always inherit a genetic disorder that is present on one of their x chromosomes?
it can be on a barr body
p53 binds to
E6
E7 binds to _____
Rb and kick off EF2, to keep it dividing
lyonization can lead to ______
mociacism
What is mosaicism?
Mosaicism is a condition where the cells of a individual have different genotypes or karyotype. The proportion or normal cells to abnormal determines the severity of the disease
Example of mosaicism
person may have 46 chromosomes in 1 cell but 47 in another
Down syndrome–> there is a trisomy of chromosome 21 in a majority of cells
mosaicism in Klinefelters
Mosaicism is a condition where the cells of 1 person can have different genotypes
For example a person with Klinefelters will have some chromosomes with 46XY but a majority with 47XXY
mosaicism in Turners Syndrom
Mosaicism is a condition where the cells of 1 person can have a different genotype
For example, in Turner’s syndrome, 1 person can have some cells with 46XX and some have 45XO
2 ways cell division can occur
mitosis and meiosis
mitosis
Cell divides and forms 2 clones of itself
goes from diploid(2n)–> diploid(2n)
Meiosis
Cell divides and produces 4 haploid cells called gametes (sperm and egg) that are NOT clones of one another. they have half the amount of DNA.
2n–>n
Mitosis has 2 phases. What happens?
- Interphase–> DNA replication occurs to create 2 chromatins attached at a centromere.
- Cell division–> will produce 2 identical daughter cells
Mitosis produces what?
2 identical diploid cells
Meiosis produces
4 non-identical haploid (n) cells
2n means what
2 copies of each chromosome
In meiosis, is genetic material kept the same or reduced?
reduced.
We go from a diploid–> haploid
Meiosis consists of ___ round of DNA replication and ____ round(s) of division
1 round of DNA replication
2 rounds of division (1 to separate the homologs and 1 to separate sister chromatids)
how does meiosis produce 4 non-identical haploid cells?
- homologous recombination–> crossing over occurs between sister chromatids of homologs
- Random segregation of homologs
Euploidy
a cell with a normal amount of chromosomes (n in haploid and 2n in diploid)
Polyploidy
3n, 4n, 5n
When there are [complete sets of extra chromosomes]
3n= 3 copies of each chromsome
Aneuploidy
individuals chromosomes are missing or added
2n+1
2n-1
Having 45 chromosomes is aneuploidy/polyploidy
aneuploidy–> individual chromosomes are missing or added
2n+1 results in a
Trisomy
What is worse in aneuploidy: having an extra or having one missing?
having a deleted one.
How do we end up in errors in DNA chromosome counting?
Non-disjunction–> the failure of homologous chromosomes to divide appropriately or sister chromatids to divide appropriately
When does the risk of non-disjunction increase?
after 35.
It rapidly accelerates after 40.
69 chromosomes: aneuploidy or polyploidy?
polyploidy because it is a multiple of 23 (3n)
What is translocation?
when non-homologous chromosomes exchange genetic information
Recipricol translocation
when non-homologous chromosomes exchange genetic information
Robertsonian translocation
when the long arms of two acrocentric chromosomes combine and the short arm is lost
Turner syndrome karyotype
45XO
People with turner syndrome are missing an X chromosome. Thus, can only be females.
Turner syndrom sx
Females have normal intelligence, but developmental delays.
Klinefelters
47XXY
Males have 1 extra X chromosome, resulting in 47 chromosomes. As the number of X’s increase, the more severe.
Klinefelters sx
Often times limited symptoms. But they could have varying degrees of [cognitive, social, behavorial and learning difficulties]
Main sx: hypogonadism (low T), small or undescended testes,
gynocomastia–> enlarged breasts
Tall
Do trisomy 13, 18 and 21 occur on sex chromosomes?
No. they are AUTOSOMAL trisomies and do not occur on sex chromosomes.
Down syndome
Trisomy 21
[47XX +21]
- There are 3 copies of chromosome 21.
- Most common trisomy
- As mother gets older, there is an increased risk
Patau syndrome
Trisomy 13
[47XX +13]
Patau syndrome results in severe developmental abnormalities and most die within 1 week (13% survive up to 10 yo)
Edwards syndrome
Trisomy 18
[47XX +18]
Abnormal development and most die within 1 week
Genomic imprinting is independent/dependent to mendelian inheritance
independent
Usually, when you inherit a gene, both copies are ____
on
In gene imprinting, instead of both copies being turned on, then?
in genomic imprinting, instead of both inherited being turned on, one is turned off through silencing
which one that is turned off is pre-determined which parent you inherited it from
how does gene silencing occr
- methylation of 5’ end
2. chromatin condensation
____ human genes are imprinted
100
___ genes are paternally imprinted, maternally expressed
30 are maternally expressed
____ genes are maternally imprinted, paternally expressed
70 are paternally expressed
In a _____ cell, imprints remain throughout life span
somatic
In ____ cells, imprints are reset at each generation.
Germ cells.
During meiosis, they’re erased and new ones are sets
Depending on which parent you get the gene from, it determines the phenotype you express when one of the genes is methylated.
a
Say you have a deletion on chromosome 15. If the deletion is on the paternal chromosome–>
If the deletion is on the maternal chromsome–>
If you inherited it from your mom–>
Deletion is on the paternal chromosome–> Prader Willie
Deletion is on the maternal chrosome–> Angelman
The phenotype of Angelman and Prader Willie depend on what?
If the chromosomal deletion is on the paternal or maternal chromosome 15
Prader Willie
short, fat, mild to moderate intellectual disability
dark vader
Angelman syndrome
severe intellectual disability
Uniparental disomy
occurs when 2 copies of a chromosome come from 1 parent; instead of 1 from mom and 1 from dad
Law of segregation
gametes receive 1 copy of a gene
law of independent assortment
genes are inherited independently of one another
Monogenic inheritance
when a trait is determined by the expression of a single gene or allele
Can people with different genotypes have 1 phenotype?
Yes
Ex. Cystic fibrosis
Can people with the same genotype have different phenotypes?
Yes
Ex. PKU
Pleiotropy
1 genotype–> different phenotypes
Ex. PKU
proband
red arrow that indicates the first dx person in the pediagree
In autosomal traits, males and females are ____ affected
in autosomal traits, males and females are equally affected.
thus, they can pass it on to a M or F
Autosomal dominant trait
- Only 1 allele is needed to express
- thus, one of your parents must have the trait
- unaffected offspring do not pass down the trait
In autosomal dominant, if you have kids with someone who is unaffected, what is the reccurent risk
50%
Autosomal recessive
- need 2 alleles
- affected individuals tend to have normal parents; skips generations
- thus, clusters around siblings
- higher in those who share genes (consanguinity-first cousin mating)
X-linked traits are more common in
men, because they only need one copy
X-linked dominant
Common?
father affected?
mother affected?
RARE DISORDERS!!!
If father is affected–> will pass down to all daughters but not sons
If mother is affected–> will pass down to 50% of daughters and 50% sons.
Are there carriers in X-linked dominant?
No. It is a dominant trait so you either have it or you dont
Ex of X-linked dominant dx
- Hypophosphotemia–> low phosphorus in blood because kidney cannot reabsorb phosphate.
difficult to reabsorb Ca2+, leading to softening of the bone –> RICKETS!
Vitamin D metabolism is abnormal
Penetrance
Frequency that a gene is expressed
Rb has a penetrance of 90%. What does this mean?
90% of people who have this gene will show the phenotype
Variable expressivity
A person with gene can show variable expressions of the phenotype.
Locus heterogenuity
Mutations at different sites can cause the same disorder
Ex. of locus heterogeneity
Osteogenensis imperfecta can be caused by a mutation at chromosome 17 or 7
What rule is used when you want to figure out the probability of an outcome of successive trials?
multiplication rule
Ex. of multiplication rule
What is the probability of having 3 boys?
What is the rule that you use when you want to figure out the probability of one outcome OR another?
addition rule
Genotype frequency
the frequency of genotypes in a population
Gene frequency is also called
allele frequency
What is gene frequency
the frequency of each allele in a population
Frequency of
M and m
HW equation tells us the relationship between
- gene frequency
2. genotype frequency
HW eqn
p+q=1
p2+2pq+q2=1
Cystic fibrosis is a ______________ ___________ disoder
autosomal recessive
you can only get it if you have [aa]
Cosanguineous (1st cousin matings) are more likely to produce kids with _______________ disorders
autosomal recessive
the mortality rate amongst children from 1st cousin mating is _____ higher
9%
Each person has ______ recessive mutations that are lethal to offspring
1-5
mT DNA
double stranded
circular
no introns
inherited directly from mother
in mT DNA, an infected mom will pass down the disorder to ______.
What about an infected dad?
mom–> all her kids
infected dad–> none
in mTDNA, mutations are ____ higher than in regular DNA. Why
10x higher
mT DNA does not have repair mechanisms and can be damaged by free radicals
Mitochondrial disorders
- LHON- lebers hereditary optic neuropathy
2. MELAS–> mitochondrial encephalopathy, lactic acidosis and stroke like episodes
LHON
lebers heriditary optic neuropathy
mitochondrial disorder
MELAS
mitochondrial encephalopathy, lactic acidosis and stroke like episodes
mitochondrial disorder
polygenic traits
polygenic traits are those that are determined by multiple genes.
Interaction of mulitple genes result in 1 trait
multifactorial inheritance
multifactorial inheritance is determined by the additive effects of many genes at different loci and also the invironment
shows familial tendency
does multifactorial inheritance show familial tendency
yes?
mulitfactorial inheritance follows what kind of curve?
bell shaped
before a multifactorial inherited gene can be expressed, what must happen?
the person must pass the threshold of liability. the threshold of liability are all of the factors that can influence the dz.
below threshold
person is normal
above threshold
person is not norla.
If a dz is more common in males, would the males have a higher or lower threshold?
lower. they are more predisposed, thus, need less risk for the gene to be displayed
the least/most affected sex will have a higher risk threshold
least
the least affected sex will transmit the dz more often to …
a person of higher risk
is the recurrent risk stable?
no, it changes from popoulation to population because gene frequencies and enironment changes
recurrence is higher/lower when:
more than one member of family is affected
higher
recurrence is higher/lower when:
expression is more severe
higher
recurrence is higher/lower when:
the proband is of the less commonly affected sex
higher
reccurent risk increases/decreases in remotely related relatives
decrreases
