What is personalized medicine?
The use of information about a patient's genotype and other clinical data in order to select a medication, therapy, etc. that is well suited to that patient.
How do you determine if a disease is genetic?
1)
An individual who exhibits a disease is more likely to have genetic relatives with the disorder than people in the general population
2)
Identical twins share the disease more often than nonidentical twins.
Identical twins are also called
monozygotic t
Concordance
The degree to which a disorder is inherited by calculating the percentage of twin pairs in which both twins exhibit the disorder relative to pairs where only one twin shows the disorder. Theoretically, for diseases caused by a single gene, concordance amo
Age of onset
For alleles that cause genetic diseases, the time of life at which disease symptoms begin to appear.
Tay-Sachs
Affected individuals appear healthy at birth but then develop neurodegenerative symptoms at 4-6 months of age. Cerebral degeneration, blindness, and loss of motor function. Typically die 3rd to 4th year in life. Typically prevalent in Ashkenazic Jews (1 o
What are the four common features of autosomal recessive disorders?
1) Frequently, an affected offspring has two unaffected parents. For deleterious alleles that cause early death or infertility, the two parents must be unaffected.
2) When two unaffected heterozygotes have children, the percentage of affected children is
Huntington Disease
Occurs during middle age
Degeneration of certain types of neurons in the brain, leading to personality changes, dementia, and early death. The mutated gene encodes a protein called huntingtin that is expressed in neurons but is also found in some cells no
What are five common features of autosomal dominant inheritance?
An affected offspring usually has one or both affected parents
However, some dominant traits show incomplete penetrance. Also, a dominant mutation may occur during gametogenesis, so two unaffected parents may produce an affected offspring.
An affected ind
Haploinsufficiency
The phenomenon in which a person has only a single functional copy of a gene, and that the single functional copy does not produce a normal phenotype. Shows a dominant pattern of inheritance because a heterozygote has the disease. Ex: aniridia -> results
Gain-of-function mutations
Such mutations change the gene product so that it "gains" a new or abnormal function. Ex: achondroplasia -> abnormal bone growth that results with short bone stature and short arms. Caused by fibroblast growth factor receptor-3 gene.
Dominant-negative mutations
The altered gene product acts antagonistically to the normal gene product. In humans, Marfan syndrome, which is due to a mutation in the fibrillin-1 gene. Fibrillin-1 gene encodes a glycoprotein that is a structural component of the extracellular matrix t
Why are males more affected than females for X-Linked Recessive Diseases?
Most X-linked genes lack a counterpart on the Y chromosome. Males are hemizygous--have a single copy--for these genes. Therefore, a female heterozygous for an X-linked recessive gene passes this trait on to 50% of her sons
ex: hemophilia
Hemophilia
A disorder in which the blood cannot clot properly after an injury. Hemophilia A is caused by a defect in an X-linked gene that encodes the protein clotting factor VIII.
What is the pattern of X-linked recessive inheritance?
1)
Males are much more likely to exhibit the trait
2)
Mothers of affected males often have brothers or fathers who are affected with the same trait
3)
Daughters of affected males produce, on average, 50% affected sons
X-linked dominant inheritance
Most male embryos die at an early stage of development so that most individuals exhibiting the disorder are females. They do not reproduce.
ex: Rett syndrome, Aicardi syndrome
1) Females are much more likely to exhibit the trait when it is lethal to males
Rett syndrome
A neurodevelopmental disorder that includes a deceleration of head growth and small hands and feet; fatal in males.
Aicardi syndrome
Unknown gene product
Characterized by the partial or complete absence of a key structure in the brain called the corpus callosum, and the presence of retinal abnormalities; fatal in males.
Vitamin D-resistant rickets
Defects in bone mineralization at the sites of bone growth or remodeling, leading to bone deformity and stunted growth in children.
Incontinentia pigmenti
Characterized by morphological and pigmentation abnormalities in the skin, hair, teeth, and nails; fatal in males.
Locus heterogeneity
Refers to the phenomenon in which a particular type of disease may be caused by mutations in two or more different genes. For example, blood clotting involves the participation of several different proteins that take part in a cellular cascade that leads
Haplotype
Refers to the linkage of alleles or molecular markers along a single chromosome. Because mutations are rare events, haplotypes do not change from one generation to the next due to new mutations. If two sites are far apart, a crossover is more likely to al
How do geneticists identify genes that cause disease when they are mutant?
The goal is to localize a disease-causing allele to a small region on a chromosome that is distinguished by its haplotype. This approach is based on:
The disease-causing allele had its origin in a single individual known as a
founder
, who lived many gene
Linkage disequilibrium
When alleles and molecular markers are associated with each other at a frequency that is significantly higher than expected by random chance.