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Flashcards in Mendelian Inheritance Deck (59):
1

Mendelian inheritance

Think "single gene inheritance"

Monogenic: single-gene

2

Law of segregation:

either tall OR dwarf

3

Law of independent assortment:

wrinkled/tall VS wrinkled/dwarf

One particular trait wasn't dependent upon another

Chromosome 1 is not dependent on chromosome 4 etc in division

4

Dystrophin and Duchenne MD

Loss of function

5

Oncogene and cancer

Gain of function

6

β-globin and sickle cell anemia

Protein alteration

7

Genotype

An individual's genetic makeup

Gene: A, a etc
Genotype: AA or Aa

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Phenotype:

What is actually observed

9

Individuals w/ distinct genotypes can have a single phenotype

Ex. Cystic Fibrosis

"Allelic heterogeneity" -can affect the expressivity of the disease

Gene can be mutated in several ways leading to various outcomes

(Just know general overview of classes)

Class 1 defect: don't get a protein even though you have the gene (most severe)

Class 2: gets made and gets outside but is desposed of because cell thinks it's garbage

Class 3: Makes way to cell surface but isn't regulated, doesn't bind well to membrane or other proteins

Class 4: Makes way to membrane but doesn't transport chloride as it should

Class 5: Underproduction: you get the protein but you just don't have enough of it (not as serious)

Class 6: recognized as not doing well and gets disposed of


10

PKU

People w/ PKU have a defective PAH enzyme so phenylalanine builds up. Normally the PAH enzyme breaks down phenylalanine. Affects person's IQ

*Individuals with the same genotype can have multiple phenotypes

11

Locus

Site on chromosome: where gene is. 2 alleles at locus

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Pedigrees: proband (propositus)

The 1st diagnosed person in pedigree

(Arrow --> donotes the proband)

13

Autosomal Dominant Inheritance

Ex. Postaxial Polydactyly

**Only 1 allele of a gene is needed for expression, 1 copy
(Aa)

Autosomal: all chromosomes except x/y, so there are 22 out of the 23

Affected offspring has one affected parent

Both males and females can transmit trait to both males and females-autosomal

Trait is expected in EVERY generation (i.e. vertical transmission)

Recurrent risk for having affected children of proband is 50%
(chance of infected person giving it to their kids-infected father+not infected mother) Aa x aa

Affected offspring have one affected parent

14

Autosomal Recessive

2 copies of a gene is needed to influence phenotype

Ex. Tyrosinase (converts tyrosine to precursor for melanin)-albinism. If enzyme is defective, you get albinism

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Autosomal Dominant vs Recessive

Dominant needs 1 copy and recessive needs 2 copies

16

Punnet Square for Autosomal Recesive Inheritance

AaxAa

25% chance of getting disease (need aa)

17

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)

18

Autosomal dominant vs Autosomal Recessive inheritance

Autosomal dominant: disease expected in every generation

19

What does consanguinity (first cousin mating) look like on pedigree chart?

Double line connecting sexual partners

20

XX

Female

21

X-linked Recessive

Males only have 1 X chromosome and females have 2

Unaffected males do not transmit the trait (no carriers)

All daughters of affected males are heterozygous carriers

Ex. Duchenne Muscular Dystrophy

22

Allele on X-chromosome in males is termed _______

Hemizygous

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X-linked recessive for women

Females can be heterozygous or homozygous

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Females passing on X-linked Recessive trait to children

Female carriers transmit the affected allele to 50% of sons and 50% of daughters

25

X-linked dominant

Ex. Hypophosphatemia (defect in the reabsorption of phosphate in kidney).

Very rare

No carriers

Males transmit the trait to only females; 100% of females (men give their Y to the son and not their X, unlike females getting both X's from parents)

Females transmit the trait to males and females; transmit to 50% of offspring (Xx x Xy)

Both males and females affected

26

Hypophosphatemia

Abnormally low levels of phosphorus in blood due to defective reabsorption of phosphate in kidney

Deficient reabsorption of Ca in intestines causes softening of bones (RIckets)

Vitamin D metabolism abnormal

Short stature: abnormally short limbs with onset

27

Reduced Penetrance

We would expect that 100% of people inheriting the genetic defect to have the problem (phenotype) but it's more like 90%

Ex. Retinoblastoma

Autosomal dominant inheritance

Phenotype occurs in 90% of individuals inheriting gene defect so 90% penetrance

28

Variable Expressivity

Describes the range of phenotypes that vary between individuals with a specific genotype

Ex. Neurofibromatosis
-Develop tumor-like growths called neurofibromas
-Patients have cafe-au-lait spots; pigmented areas the color of coffee with cream (spots differ in number, shape, size and position)

29

Locus Heterogeneity

Single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci

Also in PKU?

Ex. Osteogenesis Imperfecta
-Brittle-bone disease
-Mutations in collagen genes (2 loci; chromosome 7 and 17), either mutation exhibits the same phenotype

30

Pleiotropy

Pleiotropy occurs when one gene influences two or more seemingly unrelated phenotypic traits.

If same disease has many tissues/organ involve it is example of pleiotropy

Literally means"many turnings" -a given phenotype is carefully observed at different levels or as you said a mutation that affects multiple organs.

31

In assessing a patient with osteogenesis imperfecta, blue sclera and bone fractures were noted.these findings are example of which of the following?
1)allele hetergeity
2)locus heterogeniety
3)pleiotropy
4)multiple mutations
5)gain of functions

3)pleiotropy

32

De novo mutation

Sporadic mutation- no other affected family members

33

Pedigree: Autosomal Dominant

-Affected offspring have 1 affected parent
-Unaffected individuals do not transmit
-Trait is expected in every generation


e.g. Marfan syndrome
Huntington's disease
Retinoblastoma

34

Pedigree: Autosomal Recessive

-Affected individuals have normal parents (not infected)
-Affected individuals who mate with normal individuals tend to have normal children
-Occurence is more likely among individuals who share genes, as with consanguinity (1st cousin mating)


e.g. Cystic fibrosis
Hartnup disease
Nieman pick disease
Sickle cell disease
Werner syndrome
Xeroderma pigmentosa

35

Barr body

The X chromosome is bigger than the Y, and to keep the gene dosage equal between the sexes, X-inactivation occurs.

One X chromosome in each cell is inactivated, condensed and is known as a Barr body

36

Metacentric

Centromere in middle of chromosome

(Middle to far end)
M-->S-->A-->T

Metacentric, Submetacentric, Acrocentric, Telocentric

37

Submetacentric

centromere between the middle of the chromosome and the tip of the chromosome

(Middle to far end)
M-->S-->A-->T

Metacentric, Submetacentric, Acrocentric, Telocentric

38

Acrocentric

centromere almost at the tip of the chromosome

(Middle to far end)
M-->S-->A-->T

Metacentric, Submetacentric, Acrocentric, Telocentric

39

Telocentric

centromere at the tip of the chromosome

(Middle to far end)
M-->S-->A-->T

Metacentric, Submetacentric, Acrocentric, Telocentric

40

Short arm of chromosome

p

41

Long arm of chromosome

q

42

What does 14q32 refer to on chromosome?

14q32

Second band in the third region of the long arm of chromosome 14

43

Aneuploid

Refers to conditions when the total chromosome number is not a multiple of 23

Can arise via nondisjunction

44

Hardy-Weinberg explained

Consider two alleles, A and a, at a particular locus; aa represents a disease phenotype for an autosomal recessive disorder

a. Let p=frequency of allele A in the population

b. Let q=frequency of allele a in the population

c. p+q=1

d. If one squares p+q=1, the Hardy-Weinberg equation is realized p² + 2pq + q² = 1
(1) p² represents the frequency of AA homozygotes in the population (wild type)
(2) q² represents the frequency of aa homozygotes in the population (those with the autosomal recessive disease)
(3) 2pq represents the frequency of carriers (heterozygotes) in the population

45

Prader Willi syndrom

Inherit mutated allele from the father while the allele inherited from the mother is naturally silenced

When the paternal chromosome is deleted

Symptoms:

-Developmental delay/Mental retardation
-Hyperphagia
-Hypotonia
-Initial failure to thrive
-Distinctive facial features
-Hypogonadism
-Eating disorder

46

Angelman syndrome

Inherit mutated allele from the mother while the allele inherited from the father is naturally silenced

When the maternal chromosome is deleted

Symptoms:
-Unprovoked smiling/laughter
-Severe developmental delay/mental retardation
-Hypotonia
-Seizures
-Jerky, uncoordinated
movements
-Lack of speech

47

Imprinting

Refers to a modification of a gene's ability to be expressed via a means other than changing the base sequence of the DNA

The expression of the gene will be determined by the sex of the parent

Maternal imprinting: alleles that females modify during gamete formation

Paternal imprinting: alleles that males modify

Maternal imprinting is being interpreted to mean that alleles that are inactivated by the mother, whereas paternal imprinting is the inactivation of alleles by the father

**methylation of bases which leads to genes not being expressed

48

Genomic Imprinting

Imprinted genes=methylation=down regulated

49

Epigenetics

Study of heritable changes that do not affect the DNA sequence

50

Genetic changes

Things that can be inherited through changing DNA sequence

51

Genetics vs Epigenetics

Genetics determines WHAT is transcribed and Epigenetics determines HOW MUCH is transcribed

52

Histones and DNA

Negatively charged DNA is wrapped around positive histones

Epigenetics: determines how tight DNA is wrapped around histones

53

Mnemonic for heterochromatin and euchromatin

People from E.U tend to be more relaxed and less up-tight

54

Histone acetylation

Removes positive charge (neutralizes) --> decreases attraction to DNA

55

Methylating DNA

It's hydrophobic, so DNA will clump up

56

Mnemonic for Acetylation and Methylation

Acetylation--> Active transcription

Methylation--> genes are Missing (turn genes off)

57

Imprinting

One allele is naturally inactivated/silenced by epigenetic changes and only 1 allele is expressed

e.g. Allele from mother expressed and allele from dad silenced or vice versa

Reason it's important: if you are automatically silence one gene then that means that only one genetic defect can give you at disease (normally you have two functioning alleles but now you only have one, and no 'backup')

58

Mnemonic for Angelman Syndrome

Angels are Mother-like and Happy

Angelman syndrome leads to happiness and excessive laughter, and due to maternal mutation

59

Mnemonic for Prader-Willi

Willi is like a man's name and men usually eat more then women (hyperphagia=increased appetite)

Disease due to paternal/father's mutation