Genetic Disorders - Basics Flashcards
What are 3 categories of human genetic disorders?
- Single gene mutation - Mendelian disorders
- Chromosomal Disorders
- Complex Multigenic Disorders
What are the 3 categories of human genetic disorders?
- Single gene mutation - Mendelian disorders
- Chromosomal Disorders
- Complex Multigenic Disorders
Single gene mutations are common or uncommon and what type of penetrance do they have?
UNcommon
High penetrance
Chromosomal Disorders are common or uncommon and what type of penetrance do they have?
UNcommon
High penetrance
Complex Multigenic Disorders are common or uncommon and what type of penetrance do they have?
COMMON
LOW penetrance
What are Complex Multigenic Disorders?
Environment and multiple gene variants that interact
Is a single gene sufficient to produce disease with complex multigenic disorders?
No - need multiple and environmental factors
Permanent change in DNA
Mutation
Point mutation within a coding sequence changes?
A single base
What are the 2 types of point mutations and what do they do?
Missense - alters meaning of protein
Nonsense - stop codon
Point mutations with NON-coding sequences can be found where?
Promoter/enhancer sequences
Defective splicing
Point mutations with NON-coding sequences fail to form?
mRNA - no translation
If a deletion or insertion is a multiple of____ it will be an abnormal protein
multiple of 3
If a deletion or insertion is NOT a multiple of 3 it will be a ______ mutation
Frameshift mutation
What is a Trinucleotide repeat?
Amplification of a sequence of 3 nucleotides
Trinucleotide repeats are usually which bases?
C and G
Cytosine and Guanine
Common thing that happens with Trinucleotide repeats?
Anticipation
What is Anticipation?
- Seen with Trinucleotide repeats
= Genetic disorders passed on to next generation and symptoms become apparent earlier and are more severe
Genetic disorders become apparent at an earlier age with each generation and are more severe
Anticipation
Codominance
Both alleles contribute to phenotype
Pleiotropism
Single mutant gene creates many end effects
Genetic heterogeneity
Mutations at several loci may produce the same trait
2 Autosomal Dominant disorders that affect the nervous system?
Huntington Disease
Neurofibromatosis
3 Autosomal Dominant disorders that affect the skeletal system?
Marfan Syndrome
Ehler-Danlos Syndrome
Osteogenesis Imperfecta
1 Autosomal Dominant disorder that affects the metabolic system?
Familial Hypercholesterolemia
Familial Hypercholesterolemia has a _____ mutation
Loss of function
Huntington Disease has a _____ mutation
Gain of function
For Autosomal Dominant Disorders, is a parent usually affected and how many kids are usually affected?
Yes a parent is usually affected
50% of kids
For Autosomal Dominant Disorders, when do new mutations occur?
In germ cells of older fathers
– Unless disease decreases reproductive fitness then there will be new mutations
Incomplete pentrance
Mutation is present but normal phenotype
Variable expressivity
Trait is present but expressed differently
2 patterns of disease for Autosomal Dominant disorders?
- Regulation of metabolic pathways
2. Key structural proteins
Autosomal Dominant and Recessive - expressivity?
Dominant - variable expressivity
Recessive - uniform
Autosomal Dominant and Recessive - penetrance?
Dominant - incomplete penetrance
Recessive - complete penetrance
Autosomal Dominant and Recessive - age of onset?
Dominant - LATER
Recessive - EARLY
Autosomal Dominant and Recessive - new mutations?
Dominant - possible
Recessive - rare
What are almost all of Autosomal Recessive Disorders?
Inborn Errors of Metabolism
What is the inheritance of Cystic Fibrosis and Phenylketonuria?
Autosomal Recessive
– IEM
What chromosome has the mutation for Cystic Fibrosis?
7q31.2
What is the most common lethal genetic disease of caucasions?
Cystic Fibrosis
Do heterozygotes for cystic fibrosis have any symptoms?
They show an increased incidence of respiratory and pancreatic disease
Can other genes besides the CFTR gene manifest symptoms?
Yes - organ specific
Meconium ileus, male infertility, pancreas and lung disease is probably?
Cystic Fibrosis
What population is usually affected with phenylketonuria?
Scandinavian descent Caucasians
Phenylketonuria has a defect in? What reaction does not take place?
Defect in Phenylalanine Hydroxylase
- Cannot convert Phenylalanine to Tyrosine
(- Or Tyrosine to Melanin since there is no tyrosine!)
Symptoms of Phenylketonuria?
Hypopigmentation, intellectual disability and a musty/mousy odor to urine and sweat
With Autosomal Recessive disorders is a parent usually affects and what percentage of kids are likely to be affected?
NO parent is usually affected
- 25% of kids
If a mutation has low frequency it is likely due to?
Consanguineous marriage
X-linked Recessive Blood disorder?
Glucose - 6 - phosphate dehydrogenase deficiency
X-linked Recessive Nervous system disorder?
Fragile X Syndrome
X-linked recessive disorders affect who?
MALES
Daughters of affected males with X-linked recessive disorders are?
CARRIERS
With mitochondrial inheritance, affected females cause how many children to be affected?
ALL OF THEM
With mitochondrial inheritance, affected males cause how many children to be affected?
NONE
