Download Prenatal Genetic Diagnosis

Single gene disorder
pedigree
proband: affected individual that initially
comes to light
kindred: relatives outside of the immediate
nuclear family
siblings: brothers and sisters of the proband
Single gene disorder
Single gene disorder
single gene inheritance
autosomal dominant
autosomal recessive
X-linked dominant
X-linked recessive
Maternal (mitochondrial) inheritance
Single gene disorder
autosomal dominant: appear in every
generation; child of an affected parent has a
50% chance of inheriting the disease;
normal members do not transmit the disease
Single gene disorder
autosomal dominant: males and females are
equally likely to have the disease and to
transmit the disease; male-to-male
transmission can occur; males can have
unaffected daughters
Single gene disorder
autosomal resseive: parents of an affected
individual may not express the disease; the
chance of an affected child's brothers or
sisters having the disease are 1 in 4; males
and females are equally likely to be affected
Single gene disorder
autosomal resseive: a child is at increased
risk of a recessive disease if the parents are
related
Single gene disorder
X-linked recessive: incidence is much
higher in males than females; males do not
transmit it to their sons -- they do transmit it
to their daughters; sons of these daughters
then have a 50% chance
Single gene disorder
X-linked dominant: affected males will not
have affected sons; all of their daughters
will be affected; sons or daughters of
affected females will have a 50% chance of
getting the disease
Single gene disorder
Autosomal dominant
familial hypercholesterolemia (FHC)
Huntington's disease
acondroplasia (short-limbed dwarfism)
polycystic kidney disease
Marfan syndrome
neurofibromatosis
tuberous sclerosis
Single gene disorder
Autosomal recessive
cystic fibrosis (CF)
phenylketonuria (PKU )
alpha-1-antitrypsin (AAT ) deficiency
sickle cell anemia
ADA deficiency
Tay-Sachs disease
hemochromatosis
Single gene disorder
X-linked recessive
Duchenne muscular dystrophy
Hemophilia A
X-linked dominant: only a few, very rare,
disorders are classified as X-linked
dominant
hypophosphatemic rickets (vitamin D resistant rickets)
Multifactorial disorder
Many of the most common diseases which
affect humans undoubtedly involve
interactions of numerous genes, including
coronary heart disease, hypertension, stroke,
and various kinds of cancer.
Multifactorial disorder
Alzheimers disease
heart disease
some cancers
neural tube defects
schizophrenia
insulin-dependent diabetes mellitus
intelligence
Mitochondrial DNA-linked disorder
mitochondria contain their own private
DNA; mitochondria come only from the
egg; more than 20 hereditary disorders
maternal inheritance; fathers do not pass on
the disease
Mitochondrial DNA-linked disorder
appear at any age with a wide variety of
non-specific symptoms and signs
(metabolic disturbances, developmental
delay, blindness, hearing loss, heart rhythm
problems, short stature, and gastrointestinal
problems)
Chromosome disorder
defect is due not to a single gene, but to an
excess or deficiency of the genes contained
in a whole chromosome or chromosome
segment
Down syndrome is the most common
chromosomal disorder (1 out of 800)
Klinefelter syndrome (1 out of 1,000 males)
Turner syndrome (1 out of 5,000 females)
Chromosomal disorders
aneuploidy in oocytes (18 - 19%) and
sperm (3 - 4%)
about 1 in 13 conceptions results in a
chromosomally defective conceptus
over 50% of spontaneous abortions during
first-trimester are associated with
chromosomal anomalies
Chromosomal disorders
chromosomal defects occur in 0.65% of all
births; an additional 0.2% of babies were
born with balanced structural chromosome
rearrangements
5.6 - 11.5% of stillbirths and neonatal
deaths have chromosomal defects
Genetic disorders
2 - 3% of children are born with a
congenital birth defect
by age 18, approximately 8% are
discovered to have one or more
anomalies
Frequency of genetic disease by age
(per 1000 live births)
type
frequency by age 25
lifetime frequency
chromosome disorders
1.8
4
single-gene disorders
3.6
20
multifactorial disease
46.4
646
somatic cell (cancer)
disease
-
240
52
910
total
Chromosomal disorder
0.65 - 0.84% of all births
advanced maternal age
75 - 80% of babies with chromosomal
defects are delivered by women younger
than 35 years of age
Chromosomal disorder
> 50% of first-trimester spontaneous
abortions
> 5% of stillborn infants
Chromosomal disorder
Aneuploidy
(trisomy, monosomy, polyploidy)
Deletion
Inversion
Translocation
Insertion
Robertsonian translocation
parent
offspring
Chromosomal disorder
Incidence
Per 1000 births
Per birth
Male
1.15
1/870
Female
0.75
1/1333
1.42
1/700
Unbalanced
0.61
1/1600
Balanced
5.22
1/200
0.02
1/50,000
9.17
1/109
Sex chromosomes
Autosomal trisomy
Structural abnormality
Triploidy
Total
Type of Abnormality
Numerical aberrations
Sex chromosomes
47,XYY
47,XXY
Other (males)
47,X
47,XXX
Other (females)
Autosomes
Trisomies
13–15 (D group)
16–18 (E group)
21–22 (G group)
Other
Incidence
1/1,000 MB
1/1,000 MB
1/1,350 MB
1/10,000 FB
1/1,000 FB
1/2,700 FB
1/20,000 LB
1/8,000 LB
1/800 LB
1/50,000 LB
Type of Abnormality
Incidence
Structural aberrations
Balanced
Robertsonian
t(Dq;Dq)
1/1,500 LB
t(Dq;Gq)
1/5,000 LB
Reciprocal translocations
1/7,000 LB
Unbalanced
Robertsonian
1/14,000 LB
Reciprocal translocations and insertions 1/8,000 LB
Inversions
1/50,000 LB
Deletions
1/10,000 LB
Supernumeraries
1/5,000 LB
Other
1/8,000 LB
Total
1/160 LB