Genetic variation originates from ___.
Heritable DNA mutations
What are the four general patterns of inheritance?
1. Sex-linked (encoded on X or Y chromosome)
2. Autosomal (encoded on numeric chromosomes)
3. Recessive (both alleles must be affected for the phenotype to be conferred)
4. Dominant (a single mutant allele confers a phenotype)
Draw the following pedigree symbols:
3. Unspecified sex
4. # of children of a certain sex
6. Nonpenetrant carrier (may manifest disease)
7. Obligate carrier (will not manifest disease)
13. Monozygotic twins
14. Dizygotic twins
15. Twins, unknown zygosity
16. Pedigree with generations and individuals numbered
17. Still birth
18. Adopted into family
19. Adopted out of family
21. Spontaneous abortion
23. No offspring
24. Multiple unions
25. Pregnancy (with information)
26. Termination of pregnancy
What is the genetic constitution of an individual or locus?
What is the outward characteristics of an individual or gene product?
What is one of the alternative versions of a gene or DNA sequence at a given locus?
What is the position occupied by a gene on a chromosome?
What is a genotype with identical alleles at a given locus?
What is a genotype with different alleles at a given locus?
What is a genotype with a single allele for a given chromosome segment?
What is a genotype with two different mutant alleles at one locus?
What is an alternate genotype present in a population at >1% frequency?
What is the proportion of individuals manifesting disease?
What is the extent to which a mutation exhibits a phenotype?
What results from different mutations at one locus?
What results from mutations at different loci?
What occurs when the same mutations manifest differently among individuals?
What type of inheritance manifests only when there is no healthy allele present (for single gene disorders)?
Individuals carry ___ recessive alleles that are lethal in homozygotes.
What is an example of a recessive disease?
Sickle cell anemia
What are the major characteristics of autosomal recessive inheritance?
1. Only displayed in homozygotes
2. Appears in more than one sibling of the proband, but not in parents, offspring, or other relatives (in other words, there is clustering among siblings and absence in ancestors)
3. Males and females are affected equally
4. Parents are asymptomatic carriers
5. Parents may be consanguineous
6. The recurrence risk for siblings = 1/4
7. Carrier risk of unaffected siblings of proband = 2/3
What is a relationship resulting from common ancestry which increases the chance that both parents carry the same mutant allele?
Risk of recessive genetic disease is affected by ___, ___, and ___.
Consanguinity; inbreeding; population carrier frequency
How is the degree of relationship to the proband calculated?
Degree of relationship = n = # of uninterrupted lines between proband and target
What is the coefficient of inbreeding of a child and what does it equal?
F = 1/2(proportion of alleles in common); this is the probability a child will receive both alleles for a particular gene from the same ancestor (one from mother, one from father); the proportion of loci at which a person is homozygous or identical by descent
What is the proportion of alleles in common?
If a person is inbred through more than one line of descent, how is F calculated?
___ disorders exhibit a phenotype despite presence of a healthy allele.
What are the features of autosomal dominant inheritance?
1. For single gene disorders, a pheontype is dominant if it manifests in the heterozygote.
2. If not lethal, the phenotype is found in every generation.
3. The child of an affected parents has 1/2 risk of inheriting the disease trait.
4. Unaffected family members are unlikely to transmit the disease to offspring.
5. Males and females are usually equally affected.
A mutant allele is dominant in what 5 instances?
1. Haploinsufficieny: the single normal copy produces an insufficient quantity of the normal gene product for the requirements of the organism.
2. Dominant negative effect: the product of the inactive mutant interferes with the function of the normal gene product
3. Simple gain of function: the product of the mutant gene acquires a new or enhanced function
4. Affected gene is a tumor suppressor, resulting in a predisposition to cancer that is inherited as a dominant trait because even a single cell losing the function of the other allele is enough to cause cancer.
5. Codominance: a trait is defined by two alleles that each exhibit a phenotype