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Chapter 4
Mendelian Inheritance
35
Autosomal dominant
Hh
hh
Hh
Hh
Hh
Cc
Cc
Cc
cc
cc
Cc
CC
Cc
CC
Autosomal recessive
B
C
D
X-linked dominant
R-
Rr Rr
Rr
R-
1
2
1
2
3
4
5–6
4
3
7
8
9
1
2
3
4
5
4
10
11
12
13
14
15
16
17
18
19
20
21–23
2
1–3
I
II
III
IV
5
6
7
8
3
4
Deceased
Affected
Dizygous twins
3
Total number of children
(i.e., 3 daughters)
Monozygous twins
Adopted out
Adopted in
Heterozygous for
autosomal recessive
Heterozygous for
x-linked recessive
3
4
2
1
1
2
3
4
5
6
7
1
2
3
4
1
2
D-
Dd
d-
d-
d-
d-
DD
D-
DD
D-
IV
I
II
I
X-linked recessive
III
E
Proband
Age
38
1
2
3
Birth
order
I–IV generation
Consanguineous
union
Female
Male
Unspecified sex
Miscarriage
A
10
11
12
13
14
9
A prototype family pedigree and explanation of the various symbols. (B) Pedigree of autosomal dominant
inheritance. The disorder is observed in an equal number of females and males who are heterozygous for the mutant
gene. The characteristic family pedigree is vertical in that the disorder is passed from one generation to the next gener-
ation. (C) Pedigree of autosomal recessive inheritance. The disorder is observed in an equal number of females and males
who are homozygous for the mutant gene. The characteristic family pedigree is horizontal in that affected individuals tend
to be limited to a single sibship (i.e., the disorder is not passed from one generation to the next generation). (D) Pedigree
of X-linked dominant inheritance. The disorder is observed in twice the number of females than males. There is no father-
to-son transmission. All daughters of an affected man will be affected because all receive the X chromosome bearing the
mutant gene from their father. All sons of an affected man will be normal because they receive only the Y chromosome
from the father. (E) Pedigree of X-linked recessive inheritance. The disorder is observed only in males (affected homozy-
gous females are rare). There is no father-to-son transmission.
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36
BRS Genetics
C
E
H
I
B
D
A
F
G
J
M
L
K
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Chapter 4
Mendelian Inheritance
37
FIGURE 4-2. Selected photographs of Mendelian inherited disorders. (A) Noonan syndrome.
Photograph shows a young
boy with Noonan syndrome. See text for various physical features. (B,C,D ) Cystic fibrosis. (B) Light micrograph shows a
bronchus that is filled with thick mucus and inflammatory cells (arrow). Smaller bronchi may be completely plugged by
this material. In addition, surrounding the bronchus there is a heavy lymphocytic infiltration (*). (C) PA radiograph shows
hyperinflation of both lungs, reduced size of the heart because of pulmonary compression, cyst formation, and atelecta-
sis (collapse of alveoli) in both lungs. (D) CT scan shows dilated, thick-walled bronchi (large arrow), collapse of the right
middle lobe (small arrows) which contains dilated airways (A). (E,F,G) Hypophosphatemic rickets. (E) Photograph shows
a young girl with typical bowing of the legs. (F) Radiograph shows typical bowing of the legs, near-normal mineralization
of the bones, and pronounced widening of the epiphyseal growth plates medially at the knees (arrows). (G) Light micro-
graph shows a wide epiphyseal growth plate where the chondrocytes in the zone of proliferation do not form neatly
arranged stacks but instead are disorganized into irregular nests. (H) Rett syndrome. Photograph shows a 5-year-old girl
with the typical hand position characteristic of this disorder. (I,J,K,L,M ) Duchenne muscular dystrophy. (I) Photograph
shows a young boy with pseudohypertrophy of the calves. Note how the boy braces himself by grabbing onto nearby fur-
niture with his left hand. These patients are often late walkers. (J) Light micrograph shows fibrosis of the endomysium
(arrows) surrounding the individual skeletal muscle cells. (K) Light micrograph shows the replacement of skeletal muscle
cells by adipocytes (arrows) in the later stages of the disorder, which causes pseudohypertrophy. (L) Light micrograph
(immunofluorescent staining for dystrophin) shows intense staining at the periphery skeletal muscle cells from a normal
individual. In an individual with Duchenne muscular dystrophy, there would be complete absence of dystrophin staining.
(M)
Radiograph shows the typical appearance of a dilated cardiomyopathy with a water-bottle configuration and dilata-
tion of the azygous vein (arrow).
t a b l e
4-1
Summary Table of Major Features of Mendelian Inheritance and Mitochondrial
Inheritance*
Sex Ratio
Transmission Pattern
Other
Autosomal
Disorder is observed in an
Family pedigree is vertical (disorder
Homozygosity is generally a
dominant
equal number of females
is passed from one generation
genetic lethal
and males
to the next generation)
Nuclear inheritance
Transmission by the mother
or father
Autosomal
Disorder is observed in an
Family pedigree is horizontal
Both parents are obligate
recessive
equal number of females
(disorder tends to be limited to a
heterozygous carriers (unless
and males
single sibship)
there is uniparental disomy
or consanguinity)
Mother and father each transmit a
Nuclear inheritance
recessive allele
X-linked
Disorder is observed in twice
Family pedigree is vertical (disorder is
Males usually die (a genetic
dominant
the number of females than
passed from one generation to the
lethal)
males (unless the disorder
next generation)
Heterozygous females are
is lethal in males)
Father-to-son transmission does
mildly to overtly affected
not occur
(never clinically normal)
depending on the skew of the
X chromosome inactivation
Homozygous females (double
dose) are overtly affected
Nuclear inheritance
X-linked
Disorder is observed only in
Family pedigree shows skipped
Males are usually sterile
recessive
males (affected homozygous
generations (representing
Heterozygous females are
females are rare)
transmission through female
clinically normal but may be
carriers)
mildly affected depending on
Father-to-son transmission does
the skew of the X chromo-
not occur
some inactivation
Homozygous females (double
dose) are overtly affected
Nuclear inheritance
Mitochondrial
Disorder is observed in equal
Family pedigree is vertical (disorder
A range of phenotypes is seen
number of females and
is passed from one generation to
in affected females and
males
the next generation)
males due to heteroplasmy
Maternal transmission only
Show a threshold level of
mitochondria for disorder to
be apparent
Cells with a high requirement
of ATP are more seriously
affected
Extranuclear inheritance
*Mitochondrial inheritance will be discussed in Chapter 6
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BRS Genetics
t a b l e
4-2
Summary Table of Risk Assessment in Mendelian Inheritance and
Mitochondrial Inheritance*
Parents
Children
Autosomal
Affected heterozygous mother
50% chance of having an affected child
dominant
50% chance of having a normal child
Normal homozygous father
Affected heterozygous mother
50% chance of having an affected child
25% chance of having a normal child
Affected heterozygous father
25% chance of having a lethal condition
Affected homozygous mother
100% chance of having an affected child
Normal homozygous father
Autosomal
Normal heterozygous mother
25% chance of having an affected child
recessive
50% chance of having a normal heterozygote child (carrier)
Normal heterozygous father
25% of having a normal homozygous child (noncarrier)
66% chance of having a normal heterozygote child (carrier)
33% chance of having a normal homozygous child (noncarrier)
Affected homozygous mother
100% chance of having a normal heterozygote child (carrier)
Normal homozygous father
Affected homozygous mother
50% chance of having an affected child
50% chance of having a normal heterozygote child (carrier)
Normal heterozygous father
X-linked
Affected heterozygous mother
50% chance of having an affected daughter
dominant
50% chance of having an affected son
Normal father
Normal mother
100% chance of having an affected daughter
100% chance of having a normal son
Affected father
X-linked
Affected homozygous mother
100% chance of having a carrier daughter
recessive
100% chance of having an affected son
Normal father
Normal heterozygous mother
50% chance of having a carrier daughter
50% chance of having an affected son
Normal father
Normal mother
100% chance of having a carrier daughter
100% chance of having normal son
Affected father
Normal heterozygous mother
50% chance of having an affected daughter
50% chance of having a carrier daughter
Affected father
50% chance of having an affected son
50% chance of having a normal son
Mitochondrial
Affected mother
100% chance of having an affected daughter or son (both with
a range of phenotypes)
Normal father
Normal mother
0% chance of having an affected daughter or son
Affected father
*Mitochondrial inheritance will be discussed in Chapter 6
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Chapter 4
Mendelian Inheritance
39
t a b l e
4-3
Partial List of Single Gene Mendelian Inherited Disorders by Type
Autosomal Dominant
Autosomal Recessive
X-linked
Achondroplasia
Acrocephalosyndactyly
Adult polycystic kidney disorder
Alport syndrome
Apert syndrome
Bor syndrome
Brachydactyly
Charcot-Marie-Tooth disorder
Cleidocranial dysplasia
Crouzon craniofacial dysplasia
Craniostenosis
Diabetes associated with defects in
genes for glucokinase, HNF-1
, and
HNF-4
Ehlers-Danlos syndrome (Type IV)
Epidermolysis bullosa simplex
Familial adenomatous polyposis
Familial hypercholesterolemia
(Type IIa)
Goldenhar syndrome
Heart-hand syndrome
Hereditary nonpolyposis
Colorectal cancer (HNPCC)
Hereditary spherocytosis
Huntington disorder
Marfan syndrome
Monilethrix
Myotonic dystrophy 1 and 2
Neurofibromatosis
Noonan syndrome
Osteogenesis imperfecta (Type I & IV)
Pfeiffer syndrome
Piebaldism
Retinoblastoma
Treacher Collins syndrome
Spinocerebellar ataxia 1,2,3.6,7,
8,11,17
Uncombable hair syndrome
Von Willebrand disorder
Waardenburg syndrome
Williams-Beuren syndrome
1
-Antitrypsin
Deficiency
Adrenogenital
Syndromes
Albinism
Alpha thalassemia
Alkaptonuria
Argininosuccinic aciduria
Ataxia telangiectasia
Beta thalassemia
Bloom syndrome
Branched chain ketonuria
Childhood polycystic kidney disorder
Cystic fibrosis
Cystinuria
Dwarfism
Ehlers-Danlos syndrome (Type VI)
Erythropoietic porphyria
Fanconi anemia
Friedreich ataxia
Fructosuria
Galactosemia
Glycogen storage disorder
Von Gierke (Type Ia)
Pompe (Type II)
Cori (Type IIIa)
Andersen (Type IV)
McArdle (Type V)
Hers (Type VI)
Tarui (Type VIII)
Hemoglobin C disorder
Hepatolenticular degeneration
Histidinemia
Homocystinuria
Hypophosphatasia
Hypothyroidism
Junctional epidermolysis bullosa
Juvenile myoclonus epilepsy
Lawrence Moon syndrome
Lysosomal storage disorders
Tay Sachs
Gaucher
Niemann-Pick
Krabbe
Sandhoff
Schindler
GM1 gangliosidosis
Metachromatic
leukodystrophy
Mucopolysaccharidoses
Hurler
Sanfilippo A-D
Morquio A&B
Maroteaux-Lamy
Sly
Osteogenesis imperfecta (Type II & III)
Oculocutaneous albinism (Type I & II)
Peroxisomal disorders
Phenylketonuria
Premature senility
Pyruvate kinase deficiency
Retinitis pigmentosa
Sickle cell anemia
Trichothiodystrophy
Tyrosinemia
Xeroderma pigmentosa
Dominant
Hypophosphatemic rickets
Rett syndrome
Goltz syndrome
Incontinentia pigmenti
Orofaciodigital syndrome
Recessive
Duchenne muscular
dystrophy
Ectodermal dysplasia
Ehlers-Danlos (Type IX)
Fabry disorder
Fragile X syndrome
G6PD deficiency
Hemophilia A & B
Hunter syndrome
Ichthyosis
Kennedy syndrome
Kinky hair syndrome
Lesch-Nyhan syndrome
Testicular feminization
Wiskott-Aldrich syndrome
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