Genetic Inheritance Flashcards
(61 cards)
1
Q
Genes
A
Segments of DNA in a chromosome, Each gene occupies a specific place, or locus (plural, loci)
2
Q
Chromatid
A
One of two identical copies of a chromosome.
3
Q
Centromere
A
Connects identical sister chromatids.
4
Q
Telomere
A
Is a region at the end of a chromosome for stability.
5
Q
Human somatic cells
A
Diploid cells that are differentiated. There are over 200 types of differentiated human somatic cells.
6
Q
Gametes
A
Are haploid
7
Q
Stem cells
A
Undifferentiated cells that can divide into two diploid cells..
8
Q
Homologous chromosomes
A
Refer to pairs of chromosomes.
9
Q
karyotype
A
- Entire set of a patient’s chromosomes.
- 46 chromosomes shown in the karyotype are in each of the patient’s diploid cells, unless mosaicism occurs.
- Normal human karyotype is written 46XY.
- Each chromosome in the karyotype is presented as a single condensed or as a duplicated chromosome.
10
Q
Mosaicism
A
Is a condition in which cells from a patient have different genotypes (& karyotypes): - Downs Syndrome: some 46XX; some 47XX,+21 - Klinefelter Syndrome: some 46XY; some 47XXY - Turner Syndrome: some 46XX; some 45XO
11
Q
Lyonization
A
Is called X- inactivation. The choice of which X chromosome to be inactivated is random.
12
Q
Interphase
A
Chromosome duplication (E.C.C)
13
Q
Cell division
A
One copy of each chromosome and 1⁄2 of the cytoplasm/organelles are distributed between the two daughter cells. (E.C.C)
14
Q
Meiosis
A
Reduces the total number of chromosomes by half, producing four gametes.
Consists of: one round of DNA replication and two rounds of nuclear divisions.
15
Q
Homologous recombination (meiosis)
A
Can produce new combinations of genes.
16
Q
Non-disjunction
A
Is the failure of one or more pairs of homologous chromosomes, or sister chromatids, to separate normally during division.
17
Q
Autosomes
A
Chromosomes common
in both genders, one from each parent.
18
Q
Sex chromosomes
A
- X, female
- Y, male
19
Q
Meiosis creates genetic diversity in 2 ways:
A
- Random segregation of
homologs. - Cross-over exchange.
20
Q
Nondisjunction
Meiotic Errors
A
Homologs fail to separate properly. - Common and increase with advancing maternal age. - Cause of spontaneous abortions and mental retardation.
21
Q
Aneuploid (Meiotic Errors)
A
Cells with abnormal chromosome number. - Trisomy 21 (Down syndrome): most common cause of mental retardation. - In 90% of trisomy 21 patients, the additional chromosome is maternal. - 70% occur during MI - 30% in MII
22
Q
Euploid (Meiotic Errors)
A
Cells with normal number of chromosomes.
23
Q
Genomic Imprinting
A
- Imprinted genes = methylation = down regulated. - Two chromosomes from same parent that have parent-specific imprinting = no gene product (Deletion of non-imprinted genes).
24
Q
Two different outcomes of deletion on chromosome 15.
A
- If paternal chromosome is deleted = Prader Willi syndrome. - If Maternal chromosome deleted = Angelman syndrome.
25
Pedigree analysis
Mechanisms of inheritance from family history.
26
Gene defect
Etiology of a disease.
27
Molecular diagnosis
Disease from a patient’s tissue/fluid samples.
28
Personalized medicine
Optimal course of treatment.
29
Population genetics
Allele and disease frequency.
30
Genotype
- An individual’s genetic
makeup.
EX: Individuals with distinct
genotypes can have a
single phenotype
(Cystic Fibrosis).
31
Phenotype
```
- What is actually observed.
EX: Individuals with the
same genotype can
have multiple
phenotypes (PKU).
```
32
Pedigrees
```
- Proband (propositus): First
diagnosed person in the
pedigree.
- Arrow denotes the
proband.
- (Slide 22 & 23)
```
33
Autosomal Dominant Inheritance
```
- Only 1 allele of a gene is
needed for expression.
- Affected offspring has one
affected parent.
- Unaffected individuals do
not transmit trait.
- Males and females can
transmit trait to both males
and females – autosomal.
- Trait is expected in every
generation
- Recurrent risk is 50%
EX: Postaxial Polydactyly
```
34
Punnet Square
| for Autosomal Dominant Inheritance
```
- Affected female mates with
unaffected male.
- Combinations of alleles
from the fertilization of egg
by sperm.
(Slide 25)
```
35
Autosomal Dominant: Pedigree
```
- Affected offspring have
one affected parent.
- Unaffected individuals do
not transmit trait.
- Both males and females
can transmit trait to both
males and females.
- Trait is expected in every
generation at 50%.
(Slide 26)
```
36
Autosomal Recessive Inheritance
- 2 copies of a gene is
needed to influence
phenotype.
EXAMPLE: TYROSINASE-NEGATIVE ALBINISM
37
Punnet Square
| for Autosomal Recessive Inheritance
```
- Carrier female mates with
carrier male.
- Resulting combinations of
alleles from the fertilization
of egg by sperm.
(Slide 28)
```
38
Autosomal Recessive: Pedigree
```
- Affected individuals have
normal parents
- Recurrent risk for
heterozygote parents is
25%.
- Both males and females
may be affected.
- Affected individuals who
mate with normal
individuals tend to have
normal children.
- Occurrence is more likely
among individuals who
share genes, as with
consanguinity (first cousin
mating). (Slide 29)
```
39
X-linked Recessive
| males, one X females, two X
```
- Disease allele on X in males
is termed “hemizygous.”
- Females can be
heterozygous or
homozygous.
- Unaffected males don’t
transmit the trait (no
carriers)
- Female carriers transmit the
disease allele to 50% of
sons and 50% of daughters
- All daughters of affected
males are heterozygous
carriers.
EXAMPLE: DUCHENNE MUSCULAR DYSTROPHY
```
40
X-linked Dominant
- Very rare; no carriers.
- Males with the disease allele
transmit the trait:
- only to females
- 100% transmission
- Females with the disease
allele transmit the trait:
- To both males and females
- 50% transmission to
offspring
EXAMPLE: HYPOPHOSPHATEMIA
- Low phosphorus in blood due
to defective reabsorption of
phosphate in kidney Deficient
absorption of calcium in
intestines causes softening of
bone (Rickets)
- Vitamin D metabolism
abnormal Short stature
- Incidence: 1/60,000
Treatment: oral phosphate &
vitamin D
41
Reduced Penetrance
```
- The frequency a gene
manifests itself is called
penetrance
- In some cases, 100% of
individuals inheriting a
genetic defect show the
clinical presentation
(phenotype) of the disease
(100% penetrance)
- In other cases penetrance is
less than 100%
EXAMPLE: RETINOBLASTOMA:
autosomal dominant inheritance Phenotype occurs in 90% of
individuals inheriting gene defect; so 90% penetrance.
```
42
Variable Expressivity
```
- Term used to describe the
range of phenotypes that vary
between individuals with a
specific genotype.
EXAMPLE: NEUROFIBROMATOSIS
- Develop tumor-like growths
called neurofibromas
- Patients have café-au-lait
spots – pigmented areas the
color of coffee with cream
(spots differ in number,
shape, size and position).
```
43
Locus Heterogeneity
```
- Single disorder, trait, or
pattern of traits caused by
mutations in genes at
different chromosomal loci
EXAMPLE:
OSTEOGENESIS IMPERFECTA
- Brittle-bone disease.
- Mutations in
collagen genes (two loci:
chromosome 7 and 17),
either mutation exhibits
the same phenotype.
```
44
Basic Concepts of Probability
```
Probability helps us:
- Understand transmission
of genes thru generations.
- Analyze genetic variation
in populations.
- Conduct risk assessment
(for genetic counseling)
```
45
Probability
```
- Is defined as the proportion
of times that a specific
outcome occurs in a series
of events.
- As proportions,
probabilities are between 0
and 1.
EXAMPLE:
- coin tossing: the probability
of ‘Heads’ is 1⁄2, of ‘Tails’ is
1⁄2
- meiosis: the probability that
a given member of a pair of
chromosomes will be
transmitted is 1⁄2, the other
is 1⁄2.
- Gender: the probability of
producing a girl is 1⁄2, a boy
is 1⁄2.
```
46
INDEPENDENCE PRINCIPLE
Multiplication Rule & Addition Rule
47
MULTIPLICATION RULE
Probability of a given outcome in multiple trials is the product of the probabilities of each trial outcome.
EX: What’s the probability of producing three girls? 1⁄2 x 1⁄2 x 1⁄2 = 1/8 What’s the probability of producing three boys? 1⁄2 x 1⁄2 x 1⁄2 = 1/8
48
THE ADDITION RULE
Probability of either one outcome or another is the sum of the two probabilities.
EX: Probability of producing either three girls or three boys? 1/8 + 1/8 = 1⁄4
49
Gene & Genotype Frequencies
```
- Measure and understand
population variation in the
incidence of genetic
disease.
- Under simple conditions
these frequencies can be
estimated by direct
counting.
```
50
Gene Frequencies
Specify the proportions of each allele in a population.
51
Genotype Frequencies
Specify the proportions of each genotype in a population.
| Slide 39
52
Hardy- Weinberg Principle
```
- Specifies the relationship
between Gene Frequencies
and Genotype Frequencies
- Useful in estimating Gene
Frequencies from Disease
Prevalence Data and in
estimating the incidence of
heterozygous carriers of
recessive disease genes
- In the previous example
(MN blood group), due to
co-dominance, the three
genotypes can be easily
distinguished, blood-typed
and counted. (Slide 40 & 41)
```
53
Cystic Fibrosis
```
- In recessive disease, only
the affected homzygotes,
with genotype aa, are
distinguishable
- H-W tells us that the
frequency of aa should be
q2.
- The incidence of CYSTIC
FIBROSIS (in European
population) is 1/2500 = q2.
- Therefore, q = 1/2500 = 1/50
= 0.02
- Because p + q = 1, then p =
0.98
- 2pq equals about 1/25,
suggesting a lot of recessive
disease alleles are
effectively “hidden."
```
54
Autosomal Dominant Inheritance
Is characterized by vertical transmission of the disease phenotype, a lack of skipped generations, and roughly equal numbers of affected males and females. Father-to- son transmission may be observed.
55
Autosomal Recessive Inheritance
Is characterized by clustering of the disease phenotype among siblings, but the disease is not usually seen among parents or other ancestors. Equal numbers of affected males and females are usually seen, and consanguinity may be present.
56
Consanguineous
```
- Mating’s that are more
likely to produce offspring
affected by rare
Autosomal Recessive
Disorders.
- Studies show that
mortality rates among the
offspring of first-cousin
mating's are up to 9%
higher than those of the
general population.
```
57
Multifactorial Inheritance: Basic Model
```
- Traits in which variation is t
thought to be caused by the
combined effects of multiple
genes are called
POLYGENIC (“many genes”)
- When environmental factors
cause variation in the trait,
the term MULTIFACTORIAL
is used.
- Because these traits are
caused by the additive
effects of many genetic and
environmental factors, they
tend to follow a normal, or
bell-shaped, distribution in
populations. (Slide 45)
```
58
Multifactorial Inheritance: Threshold Model
```
- For diseases that do not
follow the bell- curve
distribution there is an
underlying liability
distribution.
- For multifactorial diseases
that are either present or
absent, it is thought that a
threshold of liability must
be crossed before the
disease is expressed.
- Below the threshold, the
person appears normal
- Above the threshold, the
person is affected by the
disease. (Slide 46)
```
59
Pyloric Stenosis
```
- Muscular hypertrophy
between stomach and
duodenum – leading to
vomiting and obstruction
- Five times more common in
males than females.
- Males need less risk genes
to show disease; females
need more risk
genes.
- The least affected sex has a
higher risk threshold and
transmits the
condition more often to the
most frequently affected
sex.
- Children of women with
pyloric stenosis are more
likely to be born with
condition (especially
males)
- Children of affected males
with pyloric stenosis are
less likely to be born with
condition.
```
60
Recurrence Risks
| And Transmission Patterns
```
- In contrast to most single-
gene diseases, recurrence
risks for multifactorial
diseases can change
substantially from one
population to another - This
is because gene
frequencies as well as
environmental factors can
differ among populations
› The recurrence risk is
higher if more than one
family member is affected
› If the expression of the
disease in the proband is
more severe, the
recurrence risk is higher
› The recurrence risk is
higher if the proband is of
the less commonly
affected sex
› The recurrence risk for the
disease usually decreases
rapidly in more remotely
related relatives
```
61
Multifactorial vs Single- Gene Inheritance
```
- Multifactorial Disease is
caused by the simultaneous
influence of multiple
genetic and environmental
factors.
- In some cases, a trait may
be influenced by the
combination of both a
single gene with large
effects and a multifactorial
background in which
additional genes and
environmental factors have
small individual effects.
(Slide 48)
```
