single gene disorder pedigree proband: affected individual that initially comes to light kindred:...
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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 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 dominantfamilial hypercholesterolemia (FHC)Huntington's diseaseacondroplasia (short-limbed dwarfism)polycystic kidney diseaseMarfan syndromeneurofibromatosistuberous 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 recessiveDuchenne muscular dystrophyHemophilia AX-linked dominant: only a few, very rare, disorders are classified as X-linked dominanthypophosphatemic 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 disordersmaternal 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 segmentDown 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
total 52 910
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
Aneuploidy
(trisomy, monosomy, polyploidy)
Deletion
Inversion
Translocation
Insertion
Chromosomal disorderIncidence Per 1000 births Per birth
Sex chromosomes
Male 1.15 1/870
Female 0.75 1/1333
Autosomal trisomy 1.42 1/700
Structural abnormality
Unbalanced 0.61 1/1600
Balanced 5.22 1/200
Triploidy 0.02 1/50,000
Total 9.17 1/109
Type of Abnormality Incidence
Numerical aberrations
Sex chromosomes
47,XYY 1/1,000 MB
47,XXY 1/1,000 MB
Other (males) 1/1,350 MB
47,X 1/10,000 FB
47,XXX 1/1,000 FB
Other (females) 1/2,700 FB
Autosomes
Trisomies
13–15 (D group) 1/20,000 LB
16–18 (E group) 1/8,000 LB
21–22 (G group) 1/800 LB
Other 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