Mendelian inheritance

Mendelian character
 Its presence and absence depends on the
genotype at a single locus
 Does not mean that the character is
programmed by only one pair of genes
 A certain genotype at one locus is necessary
and sufficient for the character to be
expressed
 ±10.000 mendelian characters
Mendelian inheritance
 Remind: dominance and recessiveness are
properties of characters, NOT genes
 Character:
 Dominant  manifest in heterozygote
 Recessive  not manifest in heterozygote
Basic Mendelian inheritance

A. Autosomal dominant
B. Autosomal recessive
C. X-linked recessive
D. X-linked dominant
E. Y-linked
What concerns...?

 Genetic counseling
 Recurrence risk

 Informed decision

 Adjustment
Autosomal dominant inheritance
Pedigree of autosomal
dominant inheritance
Features of AD inheritance
 An affected person usually has at least one
affected parent
 No skipping of generation
 Affects either sex
 Transmitted by either sex
 A child of affected x unaffected mating has a
50% chance of being affected (assuming that
the affected parent is heterozygous)
 RISK CALCULATION

Dd x dd Dd x dd

d d D d

D Dd Dd D DD Dd

d dd dd d Dd dd

Affected : unaffected ??????

1 : 1
Unusual autosomal dominant
inheritance

 Non-penetrance
 Variable expression
 Anticipation
 De novo mutation
 Genetic imprinting
 Non-penetrance
 Penetrance: the probability that a person with a
certain genotype will manifest the character
 Non-penetrance
 Failure of a dominant character to manifest

 Per definition, dominant character has 100%

penetrance  in fact??
 Continuum characters:
 Fully penetrant mendelian  multifactorials

 Complicating the genetic counseling

 Variable expression

 Different family members show

different features of the
disease/syndrome
 Waardenberg syndrome
 Hearing loss
 Different color eyes
 White forelock
 Premature graying of hair
Genetic anticipation
 The phenotype is more severe in successive
generation
 Unclear mechanism
 Myotonic dystrophy
 Huntington disease
Genetic imprinting
 Normally, genes are equally express either
from paternal or maternal copies
 Genetic imprinting: expression depends on
the origin of the gene/genes paternal or
maternal
 Paternal imprinting Prader-Willi syndrome
 Maternal imprinting  Angelman syndrome
Genetic imprinting

 The disorder manifests only when the gene is

inherited from the father
Genetic imprinting

 The disorder manifests only when the gene is

inherited from the mother
 De novo mutation

 Newly occured mutation

Autosomal recessive?
X-linked recessive?
Complicated AD pattern
What’s next...?

 Be familiar with common AD disorders

Autosomal recessive inheritance
 Features of AR inheritance
 Affected people are usually born to unaffected parents 
WHY?
 Parent of affected people are usually asymptomatic
carrier
 Increased incidence of parental consanguinity  WHY?
 Affect either sex
 After the birth of an affected child, each subsequent
child has a 25% chance of being affected
AR inheritance

affected
carrier
Complication to AR inheritance
 Common recessive conditions can give a pseudo
dominant pedigree pattern
 Blood group O may be seen in successive
generation because of repeated marriages of group
O people with heterozygotes
Complication to AR inheritance
 Complementation
 AR congenital profound hearing loss
 Two affected parents may give unaffected child
 The disorder is associated with defect in several genes
 The children will be normal whenever the parents carry
mutation in different genes
 Usher syndrome: hearing loss + retinitis pigmentosa
 Associated with defects in 8 different genes