Pedigree Analysis - Monogenic Disorders

Question 1

What are the 5 Mendelian Monogenic inheritance options?

Answer 1

Autosomal Dominant (AD)

Autosomal Recessive (AR)

X-linked Dominant (XD)

X-linked Recessive (XR)

Y-linked

Question 2

What is the Non-mendelian Monogenic inheritance options?

Answer 2

Mitochondrial

Question 3

Phenotype, gender, carrier indication symboles

Answer 3

Question 4

Familly and Children indication symboles

Answer 4

Question 5

Death, abortion, generations, merge, proband and consultanted symboles indications

Answer 5

Question 6

What kind of pedigree?

Answer 6

Autosomal dominant pedigree

VERTICAL PEDIGREE - Gain of Function

Question 7

Which genotypes will be healthy and ill?

Answer 7

AA, Aa = Disease

aa = Healthy

Question 8

What are examples for this kind of inheritance?

Answer 8

Osteogeneisis imprefecta

Achondroplasia

Huntington

Marfan syndrome

F. Hypercholesterolemia (LDLR)

Waardenburg syndrome

Question 9

What kind of pedigree?

Answer 9

Autosomal Recessive

HORIZONTAL PEDIGREE - Loss of Function

Question 10

Which genotypes will be healthy and ill?

Answer 10

AA, Aa = Healthy

aa = Disease

Question 11

What kind of pedigree?

Answer 11

Autosomal recessive inheritance with consanguineous marriage

Question 12

What are examples for this kind of inheritance?

Answer 12

Phenylketonuria (PAH: phenylalanine hydroxylase)

Albinism (tyrosinase)

Cystic fibrosis (CFTR)

Sickle cell anemia (b-globin)

Thalassaemia (b-globin)

Question 13

What kind of pedigree?

Answer 13

X-linked dominant inheritance

•The ratio of affected females to affected males is ~ 2:1

VERTICAL PEDIGREE

Question 14

What kind of pedigree?

Answer 14

X-linked dominant inheritance

•The ratio of affected females to affected males is ~ 2:1

VERTICAL PEDIGREE

Question 15

What kind of pedigree?

Answer 15

X-linked dominant inheritance

•The ratio of affected females to affected males is ~ 2:1

VERTICAL PEDIGREE

Question 16

What are examples for this kind of inheritance?

Answer 16

• Amelogenesis imperfecta (amelogenin)
• Hypophosphataemia (phosphate-regulating endopeptidase: PHEX)
• Fragile X-syndrome (FMR1)

Question 17

What kind of pedigree?

Answer 17

X-linked recessive inheritance

HORIZONTAL PEDIGREE

CRISS-CROSS PATTERN

Question 18

What kind of pedigree?

Answer 18

X-linked recessive inheritance

HORIZONTAL PEDIGREE

CRISS-CROSS PATTERN

Question 19

What kind of pedigree?

Answer 19

X-linked recessive inheritance

HORIZONTAL PEDIGREE

CRISS-CROSS PATTERN

Question 20

What are examples for this kind of inheritance?

Answer 20

Duchenne and Becker muscular dystrophy (dystrophin)

Red-green colour blindness (multiple forms)

Hemophilia A, B (coagulation factor VIII, IX)

Question 21

What kind of pedigree? Example?

Answer 21

Y-linked inheritance

VERTICAL PEDIGREE

SRY - Azoospermia

Question 22

What kind og pedigree? Example?

Answer 22

Mitochondrial (maternal) inheritance (Non-Mendelian)

Leber’s optic atrophy

Question 23

Conditional lethality: Example

Answer 23

glucose-6-phosphate dehydrogenase (G6PD) deficiency

Question 24

Penetrance - What is it?

Effecting Factors:

Answer 24

The probability of a genotype that will manifest the trait

Large population studies is needed to define the penetrance.

The proportion of persons show the expected phenotype among the people with known genotype.

Effecting Factors:

¨Other (modifier) genes, environmental effects, Age

Question 25

Calculate the Penetrance

Answer 25

5/6\*100 = 83%

Question 26

Variable Expressivity - Example?

Answer 26

Polydactyly Different amount of fingers with same genes!

Question 27

Anticipation - What is it? Example?

Answer 27

Special type of variable expressivity Worsens as generations pass on Huntington Disease

Question 28

Phenocopy - What is it? Examples?

Answer 28

Environmental conditions could induce symptoms/traits identical to a phenotype determined by a genotype ## Footnote Deafness : Rubella infection instead of eg. cx26 mutation, AR Blindness: Rubella infection, toxoplasmosis instead of Different forms of Leber's congenital amaurosis (AR)

Question 29

Answer 29

XR

Question 30

Answer 30

AD

Question 31

Answer 31

AR

Question 32

Answer 32

XD

Question 33

Answer 33

Mitochondrial (maternal)

Question 34

**_Extesions of mendalian Inheritance_** Conditional Leathality

Answer 34

**_Extesions of mendalian Inheritance_** Like favisim - G6PD upon leathal stimulus

Question 35

**_Extesions of mendalian Inheritance_** How is it marked?

Answer 35

**_Extesions of mendalian Inheritance_** small symbole in the pedgree

Question 36

**_Extesions of mendalian Inheritance_** Penetrance

Answer 36

**_Extesions of mendalian Inheritance_**

Question 37

**_Extesions of mendalian Inheritance_** Age dependent penetrance - Example

Answer 37

**_Extesions of mendalian Inheritance_** Hemochromatosis in more than 40 years old males

Question 38

**_Extesions of mendalian Inheritance_**

Answer 38

**_Extesions of mendalian Inheritance_** 5/6

Question 39

**_Extesions of mendalian Inheritance_** FACTORS EFFECTING PEDEGREE

Answer 39

**_Extesions of mendalian Inheritance_**

Question 40

**_Extesions of mendalian Inheritance_** Phenocopy

Answer 40

**_Extesions of mendalian Inheritance_**

Question 41

**_Extesions of mendalian Inheritance_** Rett Syndrome and the phenocopy of it

Answer 41

**_Extesions of mendalian Inheritance_**

Question 42

What is the genotype of 1/I ?

Answer 42

Since Hemophillias have of X-Linked Ressecive inheritance the father must be Hemizygote Dominant (XY not xY, X is the diseased one))

Question 43

What does the star means?

Answer 43

Mutated cleavage site

Question 44

What does the rhomboid with dashes means?

Answer 44

Pregnancy of unknown fetal sex

Question 45

What is Epistasis?

Answer 45

**_Epistasis_** describes how gene interactions can affect phenotypes. When two different genes contribute to a single phenotype, those genes are said to be epistatic. An allele of a gene masks or modifies the effects of alleles of one or more other genes

Question 46

What is Recessive Epistasis?

Answer 46

**_Recessive Epistasis_** Homozygote recessive genotype of a locus masks the expression of another gene. Examples- Bombay blood group, coat color of dogs or eye colors

Question 47

As you check a pedgree you notice that all of an affected female daughters offsprings are affected - 3 generations down the line (along with some males), what is the inheritance pattern based on that?

Answer 47

Mitochondrial Inheritance

Question 48

As you check a pedgree you notice that all of an affected male daughter offsprings are affected - 3 generations down the line. The male offsprings are healthy. what is the inheritance pattern based on that?

Answer 48

X-linked Dominant

Question 49

As you check a pedgree you notice that all of an affected male daughters offsprings are affected - 3 generations down the line. The male offsprings are all affected as well. what is the inheritance pattern based on that?

Answer 49

Autosomal Dominant

Question 50

As you check a pedgree you notice that one of an affected male daughters is affected. Her brothers are all healthy. The sister of that dad is healthy while all her sons are effected. what is the inheritance pattern based on that?

Answer 50

X-Linked Recessive

Question 51

As you check a pedgree you notice that all of an affected dad sons are affected. There are no females affected 3 generations down the line. what is the inheritance pattern based on that?

Answer 51

Y-Linked (It is Vertical)

Question 52

As you check a pedgree you notice that not all of an affected dad sons are affected, just one. This son's dauther is healthy but her daughter is affected. what is the inheritance pattern based on that?

Answer 52

Autosomal Recessive