Single-Gene Inheritance Flashcards
Triangle pedigree symbol
pregnancy terminated spontaneously or not
Diamond pedigree symbol
unspecified sex
Double horizontal line in pedigree
consanguinity
brackets
adopted child (into has dashed line) (out of is solid line)
Proband arrow
marks the one who instigates the disease of study in the family
What is a compound heterozygote?
genotype with 2 different mutant alleles at one locus
What is haploinsufficiency
One allele is not enough to overcome the loss of function of the other
What are the characteristics of autosomal recessive inheritance?
- Disease in homozygote
- Appears in more than one sibling of proband, but not in parents or offspring
- Male and females are equally affected
- Parents are asymptomatic
- Parents may be consanguineous
- Risk to each sibling of the proband is 25%
Coefficient of inbreeding (F)
Proportion of loci at which a person is homozygous by descent= 1/2 x coefficient of relationship
Coefficient of relationship
proportion of genes two related individuals have in common (1/2)^n
Degree of relationship (n)
corresponds to the # of uninterrupted line segments connecting
Coefficient of relationship
(1/2) ^n where n is degree of relationship= the probability of inheriting the same allele from a common ancestor
Coefficient of inbreeding
(F) =(1/2)(coefficient of relationship)
What are the characteristics of an autosomal dominant disease?
- Manifests in heterozygote
- Seen in every generation if not lethal
- Unaffected family members not likely to transmit to offspring
- Males and females equally affected
- Child of affected parents have 1 in 2 chance of inheriting
Qualifications of a dominant mutant allele
- Haploinsufficiency: the normal gene copy does not produce sufficient quantities of normal gene product for functions of the organism
- The product of inactive mutant gene interferes with normal gene function
- Product of mutant gene acquires new function
- The affected gene is a tumor suppressor
X-linked Recessive Disease Characteristics
- Incidence higher in males
- Heterozygous females are usually unaffected
- Transmitted from an affected male to 50% of his grandsons through daughters
- Males never transmit it to their sons (only give normal Y chromosome)
X-linked Dominant Inheritance Characteristics
- Affected mothers have a 50% chance of transmitting disorder to son or daughter
- Affected fathers have affected daughters but no affected sons (Y chromosome healthy)
- Affected females may have milder expression of phenotype
When a mutation occurs in the course of development then only that part of the body derived from the mutant cell may ultimately be affected
Somatic Mosaicism
When a mutation affects germ cells, the parents may be negligibly affected but multiple offspring may have uniform disease
Germline mosaicism
Prader Willi syndrome
Occurs from a microdeletion on Chromosome 15 arm q (PWS gene) inherited from the father (mother’s is silenced). Form of genomic imprinting gone wrong. Symptoms: obesity, hypogonadism, small hands, short stature, mental retardation.
Angelman syndrome
Occurs from a microdeletion on Chromosome 15 arm q (AS gene) inherited from the mother (father’s is silenced). Form of genomic imprinting gone wrong. Symptoms: wide stance and arm position, short stature, mental retardation, spasticity, and seizures.
Mitochondrial inheritance follows which principles?
- Replicative segregation through random distribution of mitochondria among daughter cells; if the proportion of diseased mito that are passed on exceed threshold=disease
- Reduced penetrance
- Variable expression
- Pleiotropy (copy # above threshold varies in different tissues affected by mutation)
- Mosaicism
