Notes for Genetics

Who knows = =

Extra DNA, why?

transposon

DAN transposon:

• cut & paste
  Retrotransposon:
• copy & paste

DNA transposon:
transpoase recognize the IR sequences and cut it out.
Form a Pre-integration complex
Jump into another site of DNA

IR: inverted repeat
TSD: target site duplication (direct repeat)

exp: © The Tn3-family of Replicative Transposons

© viralzone

Retrotransposons

Retrotransposons have shared similarity with retroviruses
Reverse transcriptase

Similar in life cycle, similar in gene structure.

Consequence of transpositon

1. Insertion of a sequence in a new site
2. Cutting of DNA strands
   Generally: mutagenic processes, generally bad in excess

Potential disadvantages:

• disruption of coding sequence
• deletion/rearrangements of the sequences
• non-allelic homologous recombination (based on similar seq contributed by transposons)
• alternative splicing
• Epigenetic alterations
• “transduction” of neighboring sequnces
• premature polyadenylation or other transcription defects

Benefits:
V(D)J recombination in vertebrates

• V(D)J recombination generates diversity in immune system
• The RAGI.RAG2 complex catalyses the programmed deletions during antibody rearrangement.

Exp a dramatic example of active retrotransposition that is “put to use” by the hose - Drophila telomeres

non-LTR retrotransposons replaces the function of the telomerase to extending the end of the linear chromosomes.

P elements, more information need

P elements are transposable elements that were discovered in Drosophila as the causative agents of genetic traits called hybrid dysgenesis. The transposon is responsible for the P trait of the P element and it is found only in wild flies. They are also found in many other eukaryotes.^[1]

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Generate Mouse models

• Spontaeous mutant starins
• chemical-induced mutatgenesis models
• Transplatntation/Engraftment models
• Transgenic and gene targeting models
• PDX mouse models.

PS: PDX can preserve the traits better than other for some reason.

Spontaneously arising mutatnt strain lethal yellow

• Maturity-onset obesity
• Adipocytehypertrophy
• hypertriglyceridemia
• Hyperinsulinemia
• Diabetes
• Hypatic lipogenesis
• Increased caloric efficiency

Chmical mutagensis mouse models

• Germline: N-ethyl-N-nitrosourea ENU (1/700 loci) (cause random mutations in sperm)
• Pancreas: Streptozotocin (destroys pancreatic β-cells), T1D
• Skin: 7,12-dimethylbenz[a]anthracene (DMBA) + TAP
• Lung: Nitrosamines
• Linve
• Bearst;
• Colon:
• Bladder

Cheap, quick, and generate lots of mutatios

• Hard to figure out where, when, and how it cause the mutation.

ENU-induced mutatgenesis generates random mutat strains

1. Gene knockout → gene1 → Phenotype 1, 2, 3
2. Genome-wide mutatgenesis → lots of lots of genes → Lots of interested phynotypes

Forward and reverse Genetic Screens

• Forward:

• Spontaneously arising

• Phynotype Screen

• Mutation phenotypes reveal gene functions

• Map the genes and identify the gen products

• Reverse genetic screen

ENU - induced mutagenesis

it oxidize the G and destroy the hydrogen bond of the G

Forward genetic screen using ENU-induced mutagenesis

Patient-dereived xenograft (PDX) Model

Plant cancers from human to growth on mouse.

HGPS

• HGPS
• Muscular dystrophy
• Cardiomyopathy
• Lipodystrophy
• Mutation from laminopathies, Laminin A

Laminin A is a structural protein that forms nuclear lamina in inner nuclear membrane nuclear lamina is importatnt for maintatining interphase nuclear architecture heterozygous C to T substitution at 1824, G608G.

Reducing LMNA gene dosage rescues Zmpste24 KO-induced progera syndrome phnetype

Sketch for CH12

Target:

1. How Regulated
2. Variaty ways for regulation
3. Chromatin in regulation
4. Epigemetic Markers
5. RNA regulation (miRNA, post-TGR)

1. Difference between the eukaryotic cells and prokaryotic cells:

• One RNA pol in prokaryotic but 3 in Eu
• Intron and exon

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1. Majumdar, S; Rio, DC (April 2015). “P Transposable Elements in Drosophila and other Eukaryotic Organisms”. Microbiology Spectrum. 3 (2): MDNA3–0004–2014. doi:10.1128/microbiolspec.MDNA3-0004-2014. PMC 4399808. PMID 26104714. ↩︎