Chapter 24 Gen Flashcards
Loss-of-function mutation
Gain-of-function mutation
Mutation changes protein so it gains a new function
Dominant Negative Mutation
Mutant gene product acts antagonistically to the wild-type gene product
Haploinsufficiency
Heterozygote has 50% of the functional protein
Thousands of human diseases have a _______ basis
genetic
When an individual exhibits a disease, the disorder is____
more likely to occur in genetic relatives than in the general population
True or False: Identical twins share the disease more often than fraternal twins
true
DIfferent populations tend to have_____
different frequencies of the disease
The disease tends to develop at the ______
age of onset
The human disorder resembles a genetic disorder_______
that has a genetic basis in another mammal
Correlation is observed between a disease and a ______
mutant human gene or a chromosomal alteration
Inheritance patterns of human diseases may be determined via
pedigree analysis
Types of Inheritance of Human Diseases and Traits
Autosomal recessive
Autosomal Dominant
X-linked Recessive
X-Linked Dominant
Y-Linked
Autosomal Recessive Inheritance
- Frequently, an affected offspring will have two unaffected
parents - When two unaffected heterozygotes have children, the
percentage of affected children is (on average) 25% - Two affected individuals will have 100% affected children
- The trait occurs with the same frequency in both sexes
Examples of Autosomal Recessive Disorders
- Albinism- tyrosinase
- Cystic Fibrosis- CFTR, a chloride transporter
- Phenylketonuria (PKU)- phenylalanine hydroxylase
- Sickle cell disease- b globin
Autosomal Recessive Disorders
Disorders that involve defective enzymes typically have an
autosomal recessive mode of inheritance
* The heterozygote carrier has 50% of the functional
enzyme
* This is sufficient for a healthy (unaffected) phenotype
Hundreds of genetic diseases are inherited this way
* In many cases, the mutant genes responsible have been
identified and characterized\
Autosomal Dominant Inheritance
- An affected offspring usually has one or both affected
parents
* Can be altered by reduced penetrance - An affected individual with only one affected parent is
expected to produce (on average) 50% affected offspring - Two affected, heterozygous individuals will have (on
average) 25% unaffected offspring - The trait occurs with the same frequency in both sexes
- For most dominant disease-causing alleles, the
homozygote is more severely affected with the disorder
Mechanisms of Autosomal Dominant Disorders
Haploinsufficiency
Gain-of-function mutations
Dominant Negative Mutation
Examples of Autosomal Dominant Disorders
- Aniridia
- Achondroplasia
- Marfan syndrome
- Familial hypercholesterolemia
X-Linked Recessive
- Males are much more likely to exhibit the trait
- The mothers of affected males often have brothers or
fathers who are affected with the same trait - The daughters of affected males will produce (on
average) 50% affected sons
Examples of X-linked recessive
Duchenne muscular dystrophy
* Hemophilia A
* Hemophilia B
* Androgen insensitivity syndrome
X-Linked Dominant Inheritance
Characteristics of such disorders are:
* Males are often more severely affected
* Females may be less affected due to wild-type copy on the
other X chromosome
* Females are more likely to exhibit the trait when it is lethal
to males
* Affected mothers have a 50% chance of passing the trait
to daughters
Examples of X-Linked Inheritance
- Vitamin D-resistant rickets
- Rett syndrome
- Aicardi syndrome
- Incontinentia pigmenti
Y-Linked Traits
All sons show the trait if father has it
* No daughters will show the trait
Examples of Y-Linked Traits
Hypertrichosis
Huntington’s DIsease
-Autosomal Dominant
-Major symptom of this disease is the degeneration of certain types of neurons-leads to personality changes, dementia, and early death (age of onset-middle age)
-Mutation in a gene that encodes for protein named huntingtin
Albinism Mechanism
Loss-of-function
PKU Mechanism
CF Mechanism
Tay-Sach’s DIsease Mechanism
WHy do X-linked recessive disorders affect males
Because the mother having both X has to give the disorder to the son who only has one X
Why does red-green color blindless affect males?
Because it is X-linked recessive, meaning that if the mom has the carrier for it she will pass it down to her son and he will have it
Why are males termed hemizygous?
Males only have a single copy of X-linked genes
Locus heterogeneity
phenomenon that a disease can be caused by mutations in two or more different genes
Everything about PKU
Screening for PKU in newborns and preventing the development of PKU
Genetic Testing
use of tests to discover if an individual carries a genetic abnormality
genetic screening
population-wide genetic testing
Amniocentesis
Fetal cells are obtained from the amniotic fluid
Chorionic Villus Sampling
Fetal cells are obtained from the chorion (fetal part of the placenta)
Pre-implantation Genetic Diagnosis
Tests are done to check for problems for patients who do IVF
Prions
Proteinaceous infectious particles
Mechanisms of prion diseases
PrPSc proteins act as a
catalyst to convert normal
proteins to the abnormal
conformation
PrPSc proteins form
aggregates in brain and
nervous system
The PrPSc proteins can
spread by excretion into
bloodstream
