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)

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2
Q

Chromatid

A

One of two identical copies of a chromosome.

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3
Q

Centromere

A

Connects identical sister chromatids.

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4
Q

Telomere

A

Is a region at the end of a chromosome for stability.

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5
Q

Human somatic cells

A

Diploid cells that are differentiated. There are over 200 types of differentiated human somatic cells.

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6
Q

Gametes

A

Are haploid

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7
Q

Stem cells

A

Undifferentiated cells that can divide into two diploid cells..

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8
Q

Homologous chromosomes

A

Refer to pairs of chromosomes.

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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.
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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
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11
Q

Lyonization

A

Is called X- inactivation. The choice of which X chromosome to be inactivated is random.

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12
Q

Interphase

A

Chromosome duplication (E.C.C)

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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)

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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.

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15
Q

Homologous recombination (meiosis)

A

Can produce new combinations of genes.

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16
Q

Non-disjunction

A

Is the failure of one or more pairs of homologous chromosomes, or sister chromatids, to separate normally during division.

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17
Q

Autosomes

A

Chromosomes common

in both genders, one from each parent.

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18
Q

Sex chromosomes

A
  • X, female

- Y, male

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19
Q

Meiosis creates genetic diversity in 2 ways:

A
  • Random segregation of
    homologs.
  • Cross-over exchange.
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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.
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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
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22
Q

Euploid (Meiotic Errors)

A

Cells with normal number of chromosomes.

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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).
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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.
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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) ```