Pedigree Mendelian Genome Trouble Flashcards
Which pedigree type can skip generations?
Autosomal recessive
Outsider rules for autosomal dominant and recessive
Dominant: unknown parents are assumed to be heterozygous
Recessive: unknown parents are assumed to be homozygous normal
Are males and females equally affected for autosomal recessive disorders? X-linked recessive?
Autosomal recessive: yes
Xlinked recessive: females more likely to be carriers than displayers of phenotype
What cell cycle stage does the Mendel’s two laws take place in?
Meiosis for both
What is Mendel’s first law of segregation state?
At meiosis, alleles separate from eachother so that each gamete receives 1 copy of each allele
What does Mendel’s second law state?
Segregation of each set of alleles in meiosis is independent of segregation of other alleles
2 principal factors that determine the inheritance patterns seen in single gene disorders
- Quality of phenotype
2. Location of gene locus
Penetrance
Probability that a gene will have phenotypic expression at all.
“All or nothing”
Gene is expressed or it isn’t.
What is a threat to Penetrance?
Age dependent mechanism.
Likelihood manifesting trait dep on age
5 threats to expressivity
PMSES
- Phenocopies
- Modifier genes
- Stochastic effects
- Environmental factors
- Sex influenced/ limitations
Allelic heterogeneity
Different Mutations of same gene/locus can similar phenotype
Pleiotropy
1 gene mutation/defect can cause multiple phenotypes
What two factors produce phenotype?
Genotype and environment
SNP error frequency
1 SNP every 1000 bp = each individual ~ 3 mil bp different
Is random variation in genome beneficial/harmful?
Almost always harmful
Minisatellite (indel)
Type of variation in genome
VNTR (variable # tandem repeats)
Randomly repeated 10-100 bp
Imp for fingerprinting
Copy number variation (CNV)
Type of variation in genome
Variation in segments of genome from 200bp-2Mbp
Can range from 1 additional copy to many (Ie: A-B-C-C-D)
Primary type of structural variation
Categories of genomic DNA sequencing and frequencies
- Single copy sequences (50%)
- Repetitive DNA (40-50%)
- Genes (introns, exons, flanking seq) (20-25%)
- Translated/protein coding seq (1.5%)
Microsatellite (indel)
Type of variation in genome
STRP (short tandem repeat polymorphisms)
Di, tri, tetra nucleotide repeats
5x10^4 per genome
Types of repetitive DNA that exist in hu genome
- Tandem repeats
2. Dispersed repetitive elements
Types of Dispersed repetitive elements
- Alu family
- ie: short interspersed repetitive elements (SINES)
- L1 family
Tandem repeats
aka “Satellite DNA”
Spread throughout the genome
Found on heterochromatic regions on ch 1, 9, 16, y
Ie: alpha satellites
Describe estimated number of genes
25,000-30,000
Retrotransposition
These repeats may cause insertional inactivation of genes and may facilitate aberrant recombination events btwn diff copies of dispersed repeats, leading to disease
Ie: nonallelic homologous recombination (NAHR)
