Pedigree Analysis - Monogenic Disorders Flashcards
What are the 5 Mendelian Monogenic inheritance options?
Autosomal Dominant (AD)
Autosomal Recessive (AR)
X-linked Dominant (XD)
X-linked Recessive (XR)
Y-linked
What is the Non-mendelian Monogenic inheritance options?
Mitochondrial
Phenotype, gender, carrier indication symboles
Familly and Children indication symboles
Death, abortion, generations, merge, proband and consultanted symboles indications
What kind of pedigree?
Autosomal dominant pedigree
VERTICAL PEDIGREE - Gain of Function
Which genotypes will be healthy and ill?
AA, Aa = Disease
aa = Healthy
What are examples for this kind of inheritance?
Osteogeneisis imprefecta
Achondroplasia
Huntington
Marfan syndrome
F. Hypercholesterolemia (LDLR)
Waardenburg syndrome
What kind of pedigree?
Autosomal Recessive
HORIZONTAL PEDIGREE - Loss of Function
Which genotypes will be healthy and ill?
AA, Aa = Healthy
aa = Disease
What kind of pedigree?
Autosomal recessive inheritance with consanguineous marriage
What are examples for this kind of inheritance?
Phenylketonuria (PAH: phenylalanine hydroxylase)
Albinism (tyrosinase)
Cystic fibrosis (CFTR)
Sickle cell anemia (b-globin)
Thalassaemia (b-globin)
What kind of pedigree?
X-linked dominant inheritance
•The ratio of affected females to affected males is ~ 2:1
VERTICAL PEDIGREE
What kind of pedigree?
X-linked dominant inheritance
•The ratio of affected females to affected males is ~ 2:1
VERTICAL PEDIGREE
What kind of pedigree?
X-linked dominant inheritance
•The ratio of affected females to affected males is ~ 2:1
VERTICAL PEDIGREE
What are examples for this kind of inheritance?
- Amelogenesis imperfecta (amelogenin)
- Hypophosphataemia (phosphate-regulating endopeptidase: PHEX)
- Fragile X-syndrome (FMR1)
What kind of pedigree?
X-linked recessive inheritance
HORIZONTAL PEDIGREE
CRISS-CROSS PATTERN
What kind of pedigree?
X-linked recessive inheritance
HORIZONTAL PEDIGREE
CRISS-CROSS PATTERN
What kind of pedigree?
X-linked recessive inheritance
HORIZONTAL PEDIGREE
CRISS-CROSS PATTERN
What are examples for this kind of inheritance?
Duchenne and Becker muscular dystrophy (dystrophin)
Red-green colour blindness (multiple forms)
Hemophilia A, B (coagulation factor VIII, IX)
What kind of pedigree? Example?
Y-linked inheritance
VERTICAL PEDIGREE
SRY - Azoospermia
What kind og pedigree? Example?
Mitochondrial (maternal) inheritance (Non-Mendelian)
Leber’s optic atrophy
Conditional lethality: Example
glucose-6-phosphate dehydrogenase (G6PD) deficiency
Penetrance - What is it?
Effecting Factors:
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
Calculate the Penetrance
5/6*100 = 83%
Variable Expressivity - Example?
Polydactyly
Different amount of fingers with same genes!
Anticipation - What is it? Example?
Special type of variable expressivity
Worsens as generations pass on
Huntington Disease
Phenocopy - What is it? Examples?
Environmental conditions could induce symptoms/traits identical to a phenotype determined by a genotype
Deafness : Rubella infection instead of eg. cx26 mutation, AR
Blindness: Rubella infection, toxoplasmosis instead of Different forms of Leber’s congenital amaurosis (AR)
XR
AD
AR
XD
Mitochondrial (maternal)
Extesions of mendalian Inheritance
Conditional Leathality
Extesions of mendalian Inheritance
Like favisim - G6PD upon leathal stimulus
Extesions of mendalian Inheritance
How is it marked?
Extesions of mendalian Inheritance
small symbole in the pedgree
Extesions of mendalian Inheritance
Penetrance
Extesions of mendalian Inheritance
Extesions of mendalian Inheritance
Age dependent penetrance - Example
Extesions of mendalian Inheritance
Hemochromatosis in more than 40 years old males
Extesions of mendalian Inheritance
Extesions of mendalian Inheritance
5/6
Extesions of mendalian Inheritance
FACTORS EFFECTING PEDEGREE
Extesions of mendalian Inheritance
Extesions of mendalian Inheritance
Phenocopy
Extesions of mendalian Inheritance
Extesions of mendalian Inheritance
Rett Syndrome and the phenocopy of it
Extesions of mendalian Inheritance
What is the genotype of 1/I ?
Since Hemophillias have of X-Linked Ressecive inheritance the father must be Hemizygote Dominant (XY not xY, X is the diseased one))
What does the star means?
Mutated cleavage site
What does the rhomboid with dashes means?
Pregnancy of unknown fetal sex
What is Epistasis?
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
What is Recessive Epistasis?
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
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?
Mitochondrial Inheritance
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?
X-linked Dominant
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?
Autosomal Dominant
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?
X-Linked Recessive
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?
Y-Linked (It is Vertical)
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?
Autosomal Recessive
