Patterns of Inheritance Flashcards
what is locus
specific location of a gene or DNA sequence on a chromosome
homozygous
carrying identical alleles for 1 or more genes
heterozygous
carrying 2 different alleles for 1 or more genes
what is heterogeneity and examples
many different genes that lead to the same phenotype
ex: hearing loss
blood clotthing disorders
blindness
the address of a gene on a chromosome
locus
short arm of chromosome
p
long arm of chromosome
q
what is a region on chromosome
each arm is subdivided into numbered regions
begin from centromere
what is a band on chromosome
in each region identified by numbers
how do you read 1q2.4
chromosome 1, long arm q, region 2, band 4
same chromosomes are
homologous
homozygous
means you inherited two identical versions of a particular gene
heterozygous
alleles are different
people who have recessive traits (blue eyes, red hair, etc.) are always ___ for that gene
homozygous
refers to a degree of correspondence or similarity
homologous
refers to an organism in which both copies of a given gene have the same allele.
homozygous
Different gene from each parent on each chromosome
heterozygous
ploidy
number
what is a diploid cell
Double the number of chromosomes found in a mature germ cell, which is a haploid cell (23 chromosomes)
Human somatic cells are diploid cells with 23 pairs of chromosomes (46 individual chromosomes)
44 somatic and two germ chromosomes (XX or XY)
germ cells
egg and sperm
haploid cells with half the number of chromosomes as the somatic cells
where do we see aneuploidy
in somatic cellsw
what is aneuploidy
abnormal number or shape
how does aneuploidy occur
during cell division when chromosomes don’t separate equally bw 2 daughter cells
when do we see a chromosomal abnormality that results in genetic disorders
due to missing or extra chromosomes
what are 3 results that can be seen with aneuploidy
Monosomic condition (only one copy of a chromosome is present instead of two; 2n - 1)
Trisomic condition (one extra copy of a chromosome; 2n + 1)
Nullisomic condition (no chromosome of that chromosome pair is present; 2n -2) - generally a lethal condition
what is a monosomic condition
only one copy of chromosome present instead of two
2n-1
what is trisomic condition
one extra copy of chromosome
2n+1
what is nullisomic condition
no chromosome of that chromosome pair present
2n-2
usually lethal
what are the most common aneuploidy
trisomy 21, 18, 13
what is a knockout mouse and what is it used for
genetically engineered mouse with specific gene(s) artificially deleted or inactivated from its genome
Knock out mice have been used to study many human diseases including cancer and hearing loss
what is cellular homeostasis
tendency of an organism/cell to regulate its internal conditions, such as the chemical composition of its body fluids, so as to maintain health and functioning, regardless of external conditions
what is a phenocopy
environmentally caused trait that mimics a genetically determined trait
mimics a genetically disorder but is not genetically transferred
what are examples of phenocopy
Thalidomide exposure
a phenocopy of phocomelia
Hair loss from chemotherapy
phenocopy of the genetic disorder alopecia
what is pleiotropy
diverse effects of one gene or gene pair on several organ systems and functions resulting in multiple phenotypic effects in the body
what is marfan’s syndrome
autosomal dom genetic disorder of connective tissue
ex of pleiotropy
symptoms of marfan’s
tall, thin, long fingers, heart problems, dislocated lenses of the eyes, speech disorders
how do we classify genetic disorders
chromosomal abnormalities (number, structure)
by single gene defect (autosomal dominant, recessive, x linked dom and recessive and y linked)
mitochondrial genetic defect
multifactorial/polygenic defects
environmental influences
how are human chromosomes grouped
size/centromere location
size of chromosomes goes
largest to smallest
subcentric/submetacentric
chrom p & q arms lengths are unequal
metacentric
2 arms of chrom roughly equal in length
acrocentric
p arm so short it is hard to observe
these are 13, 14, 21, 22, and Y
what chrom are acrocentric
13, 14, 21, 22, Y
telocentric
centromere @ end of chrom
not in humans
holocentric
entire length of chrom is centromere
in nematodes (worms) not humans
when should chromosomal studies be performed
individuals iwth multiple malformations or unknown overall diagnosis
an individual with only ____ anomalies is unlikely to have a chromosomal abnoramlity
2
chromosomal abnormalities have adverse effects on _____ parts/structures of the body
many
who would be a candidate for chromosomal abnormalities
pre or post natal onset growth deficiencies and intellectual disabilities
Would individuals with normal growth patterns, psychomotor development, and intelligence be candidates for chromosomal abnormalities
nO
what is mendelian/monogenetic inheritance
inheritance of conditions caused by mutation to a SINGLE gene
what is the first law of mendelian called
law of segregation
what is the general phenotype of people with chrom abnorm?
more than 2 systems involved and intellectual disabilities and abnormal growth patters
what proteins coded by genes are involved in function in the ear and HL
Cochlear fluid homeostasis
Ionic channels
Stereocilia morphology and function
Synaptic transmission (inner ear to CN8)
Gene regulation
one gene in a gene pair is mutated
autosomal dominant
who can pass on a AD gene
either mom or dad, whoever has the phenotype
vertical transmission
AD
What is meant by vertical transmission
each generation has a mutation
which trait is the easiest to detect
AD
affected individuals of AD are
heterozygotes
what are characteristics of AD
Vertical transmission
50% risk to offspring per pregnancy
Unaffected individuals cannot transmit the disease
Males and females equally affected
Variable expressivity and penetrance
why is AD 50% chance?
father and mom can only pass down one gene out of two , so they have a 50% chance so there is only 4 genes and 1
each of the 4 offspring had a 50% of getting the disease
what is meant by 50% risk in AD?
50% risk of passing it on to EACH person
what is meant by expressivity
severity of the condition in that affected individual
what is penetrance
frequency of occurance
usually a percentage
either you show it or you do not
penetrance
will show but in varying forms of severity
expressivity
What are characteristics of AD traits
Only one copy of the gene is needed to produce the phenotype; affected individuals are heterozygotes
Chance of occurrence per pregnancy is ½ (50%)
Vertical family pattern
Persons with the trait have a parent with the trait unless they represent a spontaneous mutation
If the line is broken it stays broken
Incomplete penetrance
Variable expressivity
Male : female = 1:1
what is an example of a variable expression of phenotype
waardenburg syndrome
Two identical copies of the gene are required
autosomal recessive
25% chance of occurrence per pregnancy
AR
which inheritance do we see carriers
AR
where is consanguinity common
AR
what pattern do we see in AR
horizontal
what is the Founder effect?
they have the same ancestor and mate within their community and a lot of the individuals carry the recessive trait
Shared genetic ancestry/limited gene pool resulting in genetic conditions seen far more commonly in certain ethnic groups
give an example of a founder’s effect
Tay Sach’s disesase, a lethal neurodegenerative disease see approx 1:31 for the general population vs Ashkenazi Jews
what are characteristics of ARtraits
Two copies of the gene are required – homozygous offspring
Chance of recurrence ¼ (25%)
Carrier (heterozygous) parents
Horizontal family pattern
Either the male or female partner can transmit the trait
Male : Female 1:1
what is an obligate carrier
both parents have to be carriers in order for the offspring to inherit the trait
Mates related to each other by blood
consanguinity
what is a pseudo dominance
A situation in which inheritance of an autosomal recessive trait mimics an autosomal dominant pattern; one recessive allele could cause expression of the trait
only in x linked inheritance of male because a male has an x and a y so if they get one bad x, there is no other x so it acts like a dominant trait
where would we see pseudo dominance
in the case of x linked recessive inheritance in male offspring
hemophilia and color blindness
when do we see x linked recessive
if the females are carriers with no sign of disease
when would we see x linked dominant
if females manifest some signs of the disorder
Traits controlled by genes on the X chromosome are defined as dominant or recessive by
the phenotype of the females
who is more affecteed by x linked disorders
males
affected males of x linked can only have
carrier daughters if recessive
when will males transmit x linked trait to daughters
if it is dominant
is there male to male transmission in x linked traits and why
NO they can only give a y
Men are _____ for all genes on the X chromosome
hemizygous
why are men hemizygous for all genes on x
because they have different chromosomes
neither hetero or homo for x chromosome
why does a gene error on x cause a disease in men
Because there is no corresponding paired X chromosome with a good gene to balance the bad gene making males affected - psuedo-dominance
why are females. only carriers in x linked recessive
corresponding paired X chromosome with a good gene to balance the bad gene, makes females only carriers
how many copies of a gene is needed to produce the phenotype in AD
one
affected individuals in AD are
heterozygotes
what is the chance of occurrence per pregnancy in AD
50%
what is expressivity in AD
variable
what is expressivity? what is penetrance?
Exp: Series of signs and symptoms that can occur in different people with the same genetic condition
Determines how much the trait affects or how many features of the trait appear in the person
Pene: Complete or incomplete
Proportion of people with a specific genotype who manifest the phenotype
what is an example of AR
cystic fibrosis
what is non complementary AR mating
both parents have the same alleles and same recessive form (deafness for ex) so all of their children will have that trait (like deafness)
each offspring has 100% chance of being affected
what is hemizygous? give an example
only one copy of a gene rather than the usual two
males because they have XY
what is multifactorial
traits resulting from the interplay of multiple environmental factors with multiple genes
most commonly associated with sporadic gene mutations
what is an example of multifactorial inheritance
oculo auricular vertebral spectrum disorder
what is an obligate carrier?
parents of children with the recessive disorder phenotype
parents are normal but carry one mutant gene with offspring that show the phenotype
what is a carrier
anyone else in a family who has one mutant gene
How is an obligate carrier and carrier represented in a pedigree
either filled in half or with a dot in the middle
what does heterozygotes for an autosomal trait mean
they are carriers but do not express the phenotype of the disorder
what is another name for mitochondrial transmission
the eve gene
why are mitochondrial traits inherited from mothers only
Because sperms shed their cytoplasm during fertilization they do not contribute mitochondria to the offspring only the mothers do
who are at risk of mitochondrial disorders
all children of mothers affected are affected
100% transmission
will children of fathers with a mitochondrial trait inherit it
no
what are examples of mitochondrial disorders
predisposition to deafness from increased susceptibility to aminoglycoside ototoxicity
can aminoglycoside be inherited
YES
What are the two main traits of mitochondrial disorders
only passed on from the mom (eve gene)
every offspring, both genders, has 100% chance of being affected
what is genomic imprinting
process which a phenotype is different depending on which parent transmits the allele
give examples of genomic imprinting
prader willi syndrome (paternal)
angelman syndrome (maternal)
what is prader willi syndrome
a genomic imprinting syndrome
from deletion of chrom 15 inherited from DAD
intellectual disabilities, obesity and uncontrollable eating, orthopedic issues in later life, doesn’t enter puberty and cannot reproduce
what is angelman syndrome
a genomic imprinting syndrome
from deletion of chrom 15 inherited fromMOM
intellectual disability, developmental delay, uncontrollable and excessive laughing, gait ataxia, seizures
what is anticipation
worsening of symptoms of a genetic disease from one generation to the next
what is allelic expansion
an increase in gene size
what causes allelic expansion
increase in the number of trinucleotide base sequences
Increasing bases to increase the gene size
allelic expansion
give an example of allelic expansion
myotonic dystrophy
what is myotonic dystrophy
muscle disease featuring an inability to relax muscles at will
autosomal dominant
vertical transmission scene with differing severity (generation 10 would be more severe than generation 1)
clinical signs of myotonic dystrophy
drooping eyelids
facial weakness
mild to severe muscle weakness
what is huntingdon’s disease
autosomal dominant
seen in ash jewish community the most
50% chance of inheritance
clinical signs of huntingdon’s disease
adult onset
loss of muscle coordination and control
deterioration of intellectual function
generally early death
what is fragile x syndrome
x linked dom pattern (varying expressivity)
tip of x chromosome has a fragile site
are both males and females affected by fragile x
yes, but males have more severe symptoms than females
clinical signs of fragile x
intellectual disability
delayed development of S/L
may have ADHD
long jaw, big head, large ears
what is the most common form of inherited intellectual disability in boys
fragile x
what is a silent mutation
a mutation but still get the end result we want (same protein)
what is nonsense mutation
causes it to make a stop protein and truncated proteins
what is a non conservative mutation
Have a mutation and end with a different protein product that is too different and cannot have the same function the protein was supposed to do
Could be conditional lethal
what is conservative mutation
Have a mutation and end with a different protein product but still gets the job done
Usually no phenotypic change
what are examples of point mutations
silent, nonsense missense
what are missense mutations
conservative and nonconservative
what is the difference between pleiotropy and chromosomal disorders
Pleiotropy is the diverse effects of one gene or gene pair on several organ systems and functions resulting in multiple phenotypic effects in the body
whereas C.D. are multiple genes or chromosomes that affect multiple systems and have adverse effects on many systems/structures and most people have intellectual disabilities and abnormal growth patterns
