19 Genetics & Development 3 Flashcards
Interpret a pedigree chart: label the image
see image
Four Rules of the Pedigree chart:
1. AD =
2. If disorder is dominant what can be inferred about parents?
3. Recessive disorder - parents?
4. X-linked?
- AD = autosomal dominant // Disease appears in both sexes equally
- If disorder is dominant = one of the parents must have the disorder
- Recessive disorder - neither parent has to have disorder because both can be heterozygous
- X-linked - Allele located only on X chromosome = recessive by definition
Looking at a pedigree chart, how could you determine if a disorder is X-linked or autosomal?
- If most males in the pedigree are affected = X-linked
- If 1/2 ratio (50/50) between M and F = Autosomal
In the image is the disorder:
A. Autosomal Dominant
B. Autosomal Recessive
C. X-linked?
Autosomal recessive
Recessive disorder - neither parent has to have disorder because both can be heterozygous
In the image is the disorder:
A. Autosomal Dominant
B. Autosomal Recessive
C. X-linked?
Autosomal Dominant
AD = autosomal dominant // Disease appears in both sexes equally
2. If disorder is dominant = one of the parents must have the disorder
In the image is the disorder:
A. Autosomal Dominant
B. Autosomal Recessive
C. X-linked?
X-linked
Allele located only on X chromosome = recessive by definition
- generally recessive in females - affects males at higher rate
Differentiate between
- autosomal dominant
- autosomal recessive,
- X-linked,
- Y-linked and
- mitochondrial inheritance patterns
- autosomal dominant: manifested ikn the heterozygous state (at least one parent is usually affected) // affects both males and females
- autosomal recessive: both alleles at given locus are mutated // trait doesnt usually affect parents // 25% risk for each child
- X-linked: generally recessive in females - affects males at higher rate
- Y-linked - only affects males (father -> son)
- mitochondrial inheritance patterns: maternal inheritance (ova contain numberous mito. within abundant cytoplasm»_space; spermatozoa)
Differentiate between
- autosomal dominant
- autosomal recessive
- X-linked,
- Y-linked and
- mitochondrial inheritance patterns
- autosomal dominant: manifested ikn the heterozygous state (at least one parent is usually affected) // affects both males and females
- autosomal recessive: both alleles at given locus are mutated // trait doesnt usually affect parents // 25% risk for each child
- X-linked: generally recessive in females - affects males at higher rate
- Y-linked - only affects males (father -> son)
- mitochondrial inheritance patterns: maternal inheritance (ova contain numberous mito. within abundant cytoplasm»_space; spermatozoa)
Differentiate between
- autosomal dominant
- autosomal recessive
- X-linked,
- Y-linked and
- mitochondrial inheritance patterns
- autosomal dominant: manifested ikn the heterozygous state (at least one parent is usually affected) // affects both males and females
- autosomal recessive: both alleles at given locus are mutated // trait doesnt usually affect parents // 25% risk for each child
- X-linked: generally recessive in females - affects males at higher rate
- Y-linked - only affects males (father -> son)
- mitochondrial inheritance patterns: maternal inheritance (ova contain numberous mito. within abundant cytoplasm»_space; spermatozoa)
Differentiate between
- autosomal dominant
- autosomal recessive
- X-linked,
- Y-linked and
- mitochondrial inheritance patterns
- autosomal dominant: manifested ikn the heterozygous state (at least one parent is usually affected) // affects both males and females
- autosomal recessive: both alleles at given locus are mutated // trait doesnt usually affect parents // 25% risk for each child
- X-linked: generally recessive in females - affects males at higher rate
- Y-linked - only affects males (father -> son)
- mitochondrial inheritance patterns: maternal inheritance (ova contain numberous mito. within abundant cytoplasm»_space; spermatozoa)
Differentiate between
- autosomal dominant
- autosomal recessive
- X-linked,
- Y-linked and
- mitochondrial inheritance patterns
- autosomal dominant: manifested ikn the heterozygous state (at least one parent is usually affected) // affects both males and females
- autosomal recessive: both alleles at given locus are mutated // trait doesnt usually affect parents // 25% risk for each child
- X-linked: generally recessive in females - affects males at higher rate
- Y-linked - only affects males (father -> son)
- mitochondrial inheritance patterns: maternal inheritance (ova contain numberous mito. within abundant cytoplasm»_space; spermatozoa)
What is Cystic Fibrosis (CF)
- (?) disorder of (?)
- affects (?) in (?) glands and in the (?) lining of the (?), (?) and (?) tracts
- Abnormally (?) secretions
- Complications such as (?), (?) insufficiency, (?), (?), (?), (?), (?)
Autosomal recessive transmission
- inherited disorder of ion transport
- affects fluid secretion in exocrine glands and in the epithelial lining of the respiratory, gastrointestinal and reproductive tracts
- Abnormally viscous (thick) secretions - obstruct organ passages
- Complications such as chronic lung disease secondary to recurrent infections, pancreatic insufficiency, steatorrhea, malnutrition, hepatic cirrhosis, intestinal obstruction, male infertility
steatorrhea is an increase in fat excretion in the stools.
Describe how mutations in the CFTR gene manifests as Cystic Fibrosis
- 6 possible CFTR defects:
Autosomal Recessive pattern of inheritance
1. No funtional CFTR protein = nonsense; frameshift; canonical splice
2. CFTR trafficking defect: Missense; Amino acid deletion
3. Defective channel regulation: Missense; AA change
4. Decreased channel conductance: Missense; aa change
5. Reduced CFTR synthesis: splicing defect; missense
6. Decreased CFTR stability: Missense; aa change
Genetic and Environmental modifiers of CF?
- Polymorphisms in genes whose products modulate neutrophil funtion in response to bacterial infections
Modifier loci for severity of pulmonary disease in CF
eg Mannose binding lectin 2 (MBL2) // transforming growth factors B1 (TGF-B1) // interferon-related development of regulator 1 (IFRD1) - Bacteria (pseudomonas aeruginosa) can colonize the lower respiratory tract; concurrent viral infections predispose to such colonization
Define trinucleotide repeat disorder
Trinucleotide repeat disorders: consist of a group of human diseases, which are a result of an abnormal expansion of repetitive sequences and primarily affect the nervous system. These occur during various stages of human development
Define multifactorial inheritance
provide examples
Multifactorial inheritance is when more than 1 factor causes a trait or health problem, such as a birth defect or chronic illness. Genes can be a factor, but other things that aren’t genes can play a part, too. These may include: Nutrition. Lifestyle
Examples of multifactorial traits and diseases include: height, neural tube defects, and hip dysplasia.
- Type 1 Diabetes
What are SNPs?
SNPs (Single nucleotide polymorphisms): DNA sequence variation occurring within a population in which G, A, T, C of the genome differ between members of the biological species or paired chromosomes
- the most common type of genetic variation among people.
- Each SNP represents a difference in a single DNA building block, called a nucleotide.
What are STRs?
Short Tandem Repeats
- Dinucleotides (CA)n (n=10-60) distributed throughout the genome
- short repeated sequences of DNA (2–6 bp) that account for approximately 3% of the human genome
What are CNVs?
Copy number variations
- DNA variation occurring in a cell with an abnormal number of copies of one or more sections of the DNA
- a circumstance in which the number of copies of a specific segment of DNA varies among different individuals’ genomes
Four diseases stemming from trinucleotide repeat mutations:
- Fragile-X syndrome
- Fragile-X tremor ataxia
- Friedreich ataxia
- Huntington disease
What is genomic imprinting?
Maternal/Paternal imprinting?
Genomic imprinting is the process by which only one copy of a gene in an individual (either from their mother or their father) is expressed, while the other copy is suppressed
Maternal imprinting: transcriptional silencing of maternal allele
Paternal imprinting: paternal allele is inactivated
What is hirschsprung disease?
Failure of ganglion cells to migrate to the wall of the colon resulting from mutation in the receptor tyrosine kinase
1/5000 live births
- Polygenic; >10 dif genes and 5 loci
-
Huntington Disease:
- transmission?
- Mutation?
Huntington disease:
- Panethnic, autosomal dominant, progressive neurodegenerative disorder
- Gene product, huntingtin, is ubiquitously expressed (function unknown)
- Normal HD alleles 10-26 CAG repeats; mutants have >36
- Instability and expansion of CAG repeats results in progressively earlier ages of onset with succedding generations (anticipation)
- Expansion of huntingtin polyglutamine tract appears to confer a deleterious novel property
- SEVERE atrophy of neostriatum = hallmark of HD
- Neuronal dysfunction, generalized brain atrophy neuronal death
What is gonadal mosaicism?
Gametes have mutated cells
