Learning Objectives Week 1 Flashcards
Mendels First Law
Law of Segregation
alleles separate in meiosis such that each gamete (egg/sperm) receives one copy from each allele pair. (Half from mom, half from dad)
Mendels Second Law
Law of Independent Assortment
segregation of each pair is independent from other alleles at other loci
X-linked (Recessive) inheritance
- No male to male inheritance
- Affected males: all daughters are carriers
- Carrier females: 1/2 sons affected, 1/2 daughters carriers
Autosomal Dominant
- (Vertical) does not skip generations
- affects males and females equally
- there IS male to male transmission
- can be sex specific (ex. prostate cancer)
Autosomal Recessive
- (Horizontal)
- one generation affected
- Consanguinity increases chances
- carriers do not have the phenotype
Inheritance Pattern in Single-Gene Disorders
(2 Factors)
-Quality of Phenotype
(Dominant vs. Recessive)
Dominant phenotype is expressed in heterozygote state ( one mutant allele can cause disease)
Recessive phenotype only seen in homozygotes
Inheritance Pattern in Single-Gene Disorders
(2 Factors)
-Location of Gene Locus
(Autosomal vs Sex Chromosome)
-chromosomal location of gene locus can be on autosome (1-22) or on sex chromosome (X or Y, probably X)
X-linked (Dominant) inheritance
- No dad to son transmission
- but 100% of daughters will get it from dad. -50% of sons will get the trait if mom has it.
- pretty rare but if dad has it than all daughters will have it as well
List Threats to Mendelian Inheritance
three things
PEP
Penetrance
Expressivity
Pleiotropy
Threats to Mendelian Inheritance
Penetrance
Think of the light swtich analogy, is it on or off?
In other words if you have the mutation are you affected by it (light on) or not affected (light off). Can have incomplete penetrance and can be age dependent.
Threats to Mendelian Inheritance
Expressivity
The light dimmer. The light is on but how “bright” is it. In other words what is the severity of the expressed phenotype. Can be affected by sex, environment, modifier genes (outside of traits genetic locus), stochastic/random effects, and phenocopies (same phenotype due to non-genetic factors)
Threats to Mendelian Inheritance
Pleiotropy
“What does the light switch control and turn on or off”
Polysystemic will cause many different phenotypic expressions in different organ systems (Ex. neurofibromatosis type I).
Monosystemic, just affects one thing specifically, not as complex.
Human Genome Organization
Genome) & (Phenotype
Genome is a record of evolutionary history, reflects different selection pressures and adaptive genomes that were retained.
Genotype + environment = selects for phenotype.
3x10^9 bp = haploid human genome, distributed on 46 chromosomes (23 pairs, 22 autosomes, 1 pair of sex chromosomes
Human Genome Organization
Random Genomic Variation
Random Genomic Variation is the fuel of evolution. Variation can have mostly deleterious affects, but some are advantages and leads to adaptation. Genetic disease is a byproduct of evolution. Roughly 30 new mutations per individual.
Human Genome Organization
Dynamic and Non-Random
Shuffling of regions at each meiosis due to recombination. Can produce somatic DNA changes as well as germ-line DNA changes.
Human Genome Organization
Frequency of SNP
There is no “one human genome” there are many. Single nucleotide polymorphisms average 1 SNP every 1000 bp between any two randomly chosen human genomes. 99.9% identical and yet 3 million differences
Human Genome Organization
List DNA Variation Types
- Insertion-deletion polymorphisms (indels)
- Single Nucleotide Polymorphisms (SNPs)
- Copy Number Variations (CNVs)
- OTHER
Human Genome Organization
(DNA Variation Types)
-indels
(indels)
-Minisatellites: tandemly repeated 10-100 bp blocks of DNA; VNTR (variable number of tandem repeats)
-Microsatellites:
di, tri, tetra-nucleotide repeats; greater than 5x10^4 per genome; STRPs (short tandem repeat polymorphisms)
Human Genome Organization
(DNA Variation Types)
-SNPs
SNPs:
- frequency of 1 in 1000bps;
- PCR detectable markers, easy to score, widely distributed
Human Genome Organization
(DNA Variation Types)
-CNVs
CNVs:
- variation in segments of genome from 200bp-2Mb
- can range from one additional copy to many
- array comparative genomic hybridization (array CGH)
Human Genome Organization
(DNA Variation Types)
-OTHERS
OTHERS:
chromosomal or larger scale variations, rearrangements, translocations; variants can also be silent (majority) or have a functional effect
Ex) extra DUF1220 is macrocephaly, autism; deletions is microcephaly and schizophrenia
Human Genome Organization
Components
- Gene Rich: Chr 19
- Gene Poor: Chr 13, 18, 21
- Stable: majority of genome
- Unstable: dynamic regions; many disease associated ( SMA Chr5q13; Digeorge Syndrome Ch22q; 12 diseases 1q21)
Human Genome Organization
euchromatic & heterochromatic
Euchromatic:
more relaxed, ( genes)genome sequencing focus, there is no completely sequenced & assembled genome; many gaps still remain in eukaryotic regions
Heterochromatic:
generally un-sequenced
Human Genome Organization
(Genomic DNA Sequence Category and Frequency
1.5% of genome is protein-coding/translation (directly coding).
20-25% of genome represented by genes (exons, introns, flanking regulatory sequences involved in gene expression).
50% “single-copy” sequences (one copy of a gene).
40-50% of genome is classes of “repetitive DNA” that get repeated many many times.