Quiz: Lecture 7 & 8 Flashcards
Patterns of Inheritance
pedigree
objective is to show the history of inherited traits through generations
- frequently rule out a certain mode of inheritance but not prove
What information must be included on the pedigree?
- proband
- race/ethnicity
- name or initials (numbers for HIPPA)
- affected status (person with trait/disease)
-age of all family members/age at death (cause of death) - adoption status
- pregnancy/abortion
-consanguinity - marriage/divorce
- date pedigree obtained
- key to shading of symbols
Proband
The person being studied
- is the consultant if relaying the history
- the first affected family member seeking help
what is an obligate carrier
both parents have to be carriers in order for the offspring to inherit the trait
pedigree construction
(look at cheat sheet)
consanguinity
mating with close relatives
degrees of consanguinity
First degree = parents
Second degree = siblings
Third degree = first cousins/aunts and uncles
Monozygotic twins
Twins that develop from a single fertilized egg (identical twins of the same gender)
why do monozygotic twins occur?
Occurs b/c of the splitting of the zygote at any stage of development
- implant separately
- each has it’s own placenta
dizygotic twins
Develop from simultaneous shedding of two ooctyes.
- fertilized by different sperm
- fraternal twins
Locus
specific location of a gene or DNA sequence on a chromosome
- chromosome number, arm, region and band
Arm: P
short arm
Arm: q
long arm
How would you read 1q2.4
Chromosome 1, long arm, region 2, band 4
Homozygous
identical allele
- same gene from each parent on each chromosome
Heterozygous
alleles are different
- different gene from each parent on each chromosome
- 1 good, 1 bad
heterogeneity
many genes can lead to the same phenotype
-for example HL/deafness has tons of genes that can result in it
Wild type allele vs Mutant allele
Wild: Normal
Mutant: Abnormal
Diplod
double number of chromosomes found in a mature germ cell
-somatic has 46 (23 pairs)
Germ cells
egg & sperm
-haploid with half the number of chromosomes (23)
Aneuploidy
abnormal number of chromosomes, can be extra or missing
what are 3 results that can be seen with aneuploidy
- Monosomic condition
- Trisomic condition
- Nullisomic condition
Monosomic condition
only one copy of chromosome present instead of two
2n-1
Trisomic condition
one extra copy of chromosome
2n+1
Nullisomic condition
no chromosome of that chromosome pair is present
- this is usually lethal
2n-2
Most common aneuploidy
Trisomy 21,18, & 13
knockout mouse
genetically engineered mouse with specific genes artificially deleted
cellular homeostasis
tendency of a cell or organisms to regulate its internal conditions, such as chemical composition of body fluids, to maintain health and functioning regardless of external conditions
phenocopy
environmentally caused trait that mimics a genetically determined traits
-mimics genetic condition but not inherited
-ex. hair loss from chemotherapy can mimic the phenotype of alopecia
pleiotropy
when one gene influences two or more seemingly unrelated phenotypic traits.
- when ONE gene exhibits multiple phenotypic expressions
-all syndromic due to affecting multiple organs
Example of Pleiotropy
Marfan’s Syndrome
genetic disorder of connective tissue (that develops into a lot of things within the body)
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 (spontaneous mutation)
how are human chromosomes grouped
size (largest to smallest)/centromere location
subcentric or submetacentric
the chromosomes p and q arms are unequal lengths
metacentric
the two arms of chromosomes are roughly equal in length
acrocentric
p arm is so short its hard to see, but still present
what chromosomes in humans are acrocentric?
chromosomes 13,14,15,21,22,& Y
telocentric
the centromere is located at the terminal end of the chromosomes
-not present within humans
holocentric
entire length of the chromosome acts as the centromere
-found within worms and not within humans
an individual with only ____ anomalies is unlikely to have a chromosomal abnoramlity
2
who would be a candidate for chromosomal abnormalities
people who have pre or post natal onset growth deficiencies and intellectual disabilities
who would NOT be a candidate for chromosomal abnormalities
individuals with normal growth patterns, psychomotor development, & intelligence
Mendelian/Monogenetic Inheritance
inheritance of conditions caused by mutation of a SINGLE gene
-has 2 laws (segregation and independent assortment)
1st law
law of segregation
-pairs of homologous chromosomes separate in meiosis so that only one chromosome from each pair is present in each gamete.
- Each parent passes a randomly selected gene copy to his/her offspring
2nd law
law of independent assortment
-separate genes for separate traits are passed from parents to offspring independently of one another
-biological selection of one gene has nothing to do with the selection of the other gene
What are some functions of the proteins encoded by genes that are related to hearing loss?
1) Cochlear fluid homeostasis
2) Ionic channels
3) Stereocilia morphology and function
4) Synaptic transmission
5) Gene regulation
Most cases of genetic deafness recognized today are _____ disorders caused by mutation of ____ gene(s) and broadly classified by __________
1 ) Monogenic
2) Single
3) Mode of inheritance
autosomal dominant (AD)
you only need one bad gene to show the phenotype
-the bad gene “overpowers” the good gene to cause an abnormal phenotype
-mom or dad can pass it down
-affected people are heterozygous
autosomal dominant (AD) characteristics
- 50 % risk to offspring per pregnancy
- vertical transmission (each generation will have it)
-unaffected individuals cannot transmit the disease
-males and females are affected equally
-variable expressivity and penetrance
In autosomal dominance, what does expressivity refer to?
the severity of the genetic condition for the affected individuals
-how it expressed
In autosomal dominance, what does penetrance refer to?
frequency of occurrence; expressed as a percentage
-some can manifest later in life
-some could appear to have skipped a generation because they are carriers
What is D and d?
D=Dominant
d=recessive
Dominant:
DD
Dd
dd
DD = homozygote (affected)
Dd = heterozygote (affected)
dd = homozygote (not affected)
autosomal recessive
two identical copies of the bad gene are needed to show the phenotype
Recessive:
RR
Rr
rr
RR = homozygous (hearing)
Rr = heterozygous (hearing/carrier)
rr = homozygous deaf
characteristics of AR
- 25% chance per pregnancy
- obligate carrier (heterozygous); both parents have to be carriers for offspring to inherit
- Horizontal pattern (same generation affected, but not others)
- consanguinity is common
- males and females affected equally
- Founder effect
what is the Founder effect?
Shared genetic ancestry/limited gene pool resulting in genetic conditions seen far more commonly in certain ethnic groups
ex. Tay Sach’s disease
Complementary mating (AR)
Both parents carry a gene for a disorder, but the genes are different and don’t go together, so the kids don’t have the disorder.
- seen on a pedigree when both parents are affected but children are not
non complementary mating (AR)
When both parents carry same gene for a disorder there kids will automatically get disorder
- seen on a pedigree when both parents are carriers and children end up affected
psuedo dominance (AR)
inheritance of a recessive trait mimics a dominant pattern; one recessive allele could cause expression of the trait
- occurs in x-linked recessive inheritance of male offspring
Examples of pseudo-dominance
-Hemophilia
-Color blindness
X-linked recessive
If females are carriers with no sign of disease
X-linked dominant
If females manifest some signs of the disorder
X-Linked recessive characteristics
- no male to male transmission
- All daughters of a male with the trait will become carriers (men can only pass x to daughter) - 100%
- Carrier daughters have a 50% chance to have abnormal sons, 50% chance for normal offspring, & a 50% chance of having a carrier daughter
In an x-linked recessive (from mother) inheritance what happens if the son inherits bad x
even though it is recessive they don’t have a good X to balance out so they will automatically have the condition.
X-linked dominant characteristics
if father is affected each female offspring 100% risk
If mother is affected 50% risk (she has two x’s to give)
What are some examples of X-linked recessive inheritance?
1) Color blindness
2) Hemophilia
3) X-linked hearing loss with stapes gusher
4) Muscular dystrophy (Duchenne-type)
What is the difference between X-linked recessive and X-linked dominant
If females are carriers with no sign of disease - X-linked recessive
If females manifest some signs of the disorder - X-linked dominant
Hemizygous
men are neither heterozygous nor homozygous they only have a single X chromosome so they have only one copy of any gene on the X chromosome
What is it called when a gene error in the X chromosome will cause disease in men because there is no corresponding paired X chromosome with a good gene to balance the bad gene making males affected?
Pseudo-dominance
True or False: females are more severely affected than males in X-linked disorders
False
in an X-linked dominant inheritance, what happens to the son if the father is affected?
The son should be unaffected because the father can only pass a Y down
In a X-linked dominant inheritance, what happens to the daughter(s) if the father is affected
the daughter will be affected bc a father can only pass a daughter a X, and because it’s dominant it only needs one bad gene
True or false: X-linked dominant is very common
False
X-Linked Dominant Transmission Trait
-Chance of transmission from mother to son and daughter; both genders will be affected (50%)
-Transmission from affected father to daugher (100%)
-NO transmission from affected father to son
Y-linked Inheritance
expressed only to male offspring because the father has to pass the Y to the son
- No father to daughter transmission
- abnormal male sexual devlopement
Why are Y-linked traits only expressed to male offspring?
1) All males are hemizygous for all genes on the Y chromosome
2) No balancing of the mutant Y gene by X or another Y gene on the Y chromosome
multifactorial inheritance
Traits as a result of multiple environmental factors with multiple genes
-Most commonly associated with sporadic gene mutations
example of multifactorial inheritance
Oculo-Auricular Vertebral (OAV) spectrum disorder
-Consists of 3 rare disorders that may be intimately related to each other
polygenic inheritance
traits or diseases caused by the impact of many different genes
-each gene has a small individual impact on the phenotype
-these traits are quantitative meaning the more genes involved, the more severe the manifestation will be
-example is cleft lip/palate
Mitochondrial inheritance
the eve gene
- vertical pattern from mom
-no children of fathers with the trait will inherit it (0%)
-ALL children of an affected mother will be affected (100%)
How to identify Mitochondrial inheritance
Looking at the pedigree you will see a vertical pattern (all generations will have it)
- Only mom if affected and ALL of her children will be affected
why can’t men contribute in mitochondrial inheritance?
During meiosis the sperm sheds the mitochondria, so during fertilization the sperm as no cytoplasm so it has to come from the mother
When should we suspect a mitochondrial disorder?
A wide variety of dysfunction in multiple organ systems should raise suspicions of a mitochondrial disorde
True or false: mitochondrial DNA (mtDNA) has a slower spontaneous mutation rate than DNA in nuclear genes
FALSE: it is higher because mtDNA evolves 5 to 10 times more rapidly than genomic DNA
Examples of mitochondrial inheritance
Leber’s hereditary optic neuropathy
- sudden loss of central vision and optic nerve damaged at20 years of age
Genomic Imprinting
process in which the phenotype differs depending upon which parent transmits a particular allele or chromosome
-phenotype will vary based on if it’s from mom or dad
-it is the same gene mutation but will result in a different phenotype
Example of Genomic Imprinting
deletion of chromosome 15 will result in prader willi syndrome (paternal origin) and angelman syndrome (maternal)
anticipation
due to allelic expansion, severity will get worse
-worsening of symptoms of a genetic disease from one generation to the next
allelic expansion
Increase in gene size
-Caused by an increase in the number of tyrinucleotide base sequences
what are examples of allelic expansion and anticipation
huntington’s disease (AD pattern)
-gene on tip of chromosome 4p
normal: has 6-37 copies
affected: has 35-121 copies
consanguinity is an issue in _____ transmission and NOT an issue in ____
AR, AD
If there are carriers involved it is NOT a _____ transmission
AD
why are y-linked patterns rare?
the y chromosome is the smallest chromosome with a small amount of genes
if you see carriers on a pedigree, what does this indicate right away?
it is a recessive type of inheritance
-it CANNOT be AD
what is an important characteristic about chromosomal abnormalities?
they affect multiple systems
X-linked dominant vs autosomal dominant
in an x-linked dominant there is NO father to son transmission, AD can be passed from all parents to offspring
