Midterm Flashcards
What was the “one gene hypothesis” and did it turn out to be correct?
- one gene makes one protein
- Thought - Human Genome Project will provide the blueprint for everything
• No. Not correct - 300,000 + proteins (not that many genes)
SNPs and other mutations, were thought to be the sole cause of human variation, was this assumption correct?
Negative. (gen. occur in non-coding region)
• Of all mammalian species, humans have the least genetic variation from one another
• Our phenotypic expression. however seems to be greater than in any other mammalian species
Phenotypic expression must largely be a result of both gene regulation, and the epigenome
How much of the Human Genome is protein coding? How much is RVS?
- 4% of the Genome is protein coding
- most of the rest regulates that 4%.
- 1.5-5% of the DNA is HIGHLY conserved, being found unchanged even in the simplest organism
- 10% of the code is made of VIRAL start sequences ie endogenous RETROVIRUS SEQUENCES (RVS)
In what people and country does most of the variability in the human genome still reside?
San Bushmen of Africa: 90% of all diversity
How are mitochondrial DNA and Y chromosome DNA different, and how are they used in migration studies?
- mtDNA changes at a fairly constant rate over time - estimates AGE of a species
- Y chromosome SNP’s occur in a sequential manner throughout generations. Allows for tracing human MIGRATION patterns over the last 50,000 years
• Comparing the mtDNA “age” with the number of mutations on the Y chromosome, the timeframe and direction of migration was determined
What were the three main problems with trying to determine the cause vs. correlation in genetic disease with genetic studies like the Genome Wide Association Study (GWAS)
Correlation does not = causation
The variant may be important in disease causation
Or:
1) CHANCE - association found by random chance
2) LINKAGE - association is a result of bias in the study (linkage disequilibrium - where the variant is situated close to the disease causing segment, but does nothing in and of itself)
3) STRATIFICATION - Population stratification (an ethnic group has a concentration of the variant, and the disease, though the two aren’t linked)
Know the 5 points of control and how they work
- Chromatin Stage: DNA tightly wound up. A+T pair C+G pair
Regulation:
• Methylation of Cytidine in CpG islands - down regulates transcription
• Histone modification: addition of acetyl group prevents condensation and promotes transcription. Methylation also stimulates transcription by making accessible.
• Exon shuffling: different parts that get kept - Transcriptional Stage: Transcription is the first step of gene expression, in which a particular segment of DNA is copied into RNA by the enzyme RNA polymerase.
Regulation:
• Promoters and enhancers upstream, includes TATA and CCAAT boxes.
• DNA bends over to connect regions.
• Transcription factors bind and transcription of DNA to RNA starts - Translational Stage: Translation is the process through which cellular ribosomes manufacture proteins, in which messenger RNA (mRNA) is sequentially decoded by transfer RNA (tRNA).
Regulation:
• 5’ cap and the 3’ poly(A) tail added to mRNA
• Introns removed, exons spliced
• 5’ cap and the 3’ poly(A) tail of mRNA come together and enhancement translation - Post translational control into cytoplasm
Some RNAs and proteins go out through nuclear pores complexes (importins and exportins) into cytoplasm - Post translational modification: the protein is modified, by folding, cutting or other processes like adding functional groups, phosphorylation.
Regulation steps most important! What causes things to be coded.
TATA and CCAAT boxes are examples of what
Promoters
What is exon shuffling, and which part exon or intron remains as a section of the mRNA?
Exon shuffling is a molecular mechanism for the formation of new genes. (2+ exons from different or same genes brought together to create new exon-intron structure)
Exon sequences appear in MATURE transcripts
EXONS remain as a section of mRNA
What is the role of enhancers found in regulation of transcription?
Enhancer sequences are regulatory DNA sequences that, when bound by specific proteins called transcription factors, enhance the transcription of an associated gene.
MC form of gene control
the activity of transcription factors allows genes to be specifically regulated during development and in different types of cells.
What are the 3 major types of molecular groups that modify histones and cause epigenetic effects?
Methyl
Acetyl
Phosphate
Which epigenetic marker can attach to DNA directly?
Methyl
When looking at a cartoon or ideogram of a chromosome, how can you tell the locus from the gene? (essentially know the abbreviations for each. For instance is EPO the gene or the locus?)
Gene - sequences that code for proteins (in classical medical genetics) - named as acronyms of discoverers ie EPO
Locus - The exact physical location of a gene on a chromosome. Same for all people.
marked by “p” or “q” followed by a number.
EPO is a gene with a loci of q21.13, for example
What are DNA Marker Alleles? Are they necessarily involved in transcription or biologically active?
DNA Marker Alleles don’t necessarily have any function at all
they can be detected in the lab by southern blotting or PCR
What is the difference between the Genotype and the Phenotype?
Phenotype: what is trait or protein is coded, observable trait - our phenotypic expression seems to be greater than in any other mammal = most variation of REGULATION!
Genotype: base pair sequence
Humans have the least genetic variation from one another.
What are the 5 basic modes of inheritance for single-gene disease?
- autosomal dominant
- autosomal recessive
- X- linked dominant
- X-linked recessive
- mitochondrial
What is mitochondrial inheritance?
The locus is on the mitochondrial “chromosome”
What is autosomal recessive inheritance?
The locus is on an autosomal chromosome and BOTH alleles must be mutant alleles to express the phenotype
What are autosomal recessive pedigree characteristics?
- clinically expressed only in the homozygous state, the offspring must inherit one copy of the disease causing allele from each parent
- In contrast to autosomal dominant disease, autosomal recessive disease are typically seen in only one generation of a pedigree
- Because these genes are located on autosomes, males and females are affect in roughly equal frequencies
X-linked dominant inheritance
The locus is on the X chromosome
only one mutant allele is required for expression of the phenotype in females
Autosomal dominant inheritance
Autosomal dominant inheritance - The locus is on an autosomal chromosome (1-22)
only one mutant allele is required for expression of the phenotype
X-linked recessive inheritance
The locus is on the X chromosome and both alleles must be mutant alleles to express the phenotype in females
These are pedigree characteristics of what?
• affected individuals receive a disease causing gene from ONE affected parent
- the disease is typically observed in sequential generations (Skipped generations are not typically seen because two unaffected parents cannot transmit a disease causing allele to their offspring (an exception occurs when there is reduced penetrance))
• Because these genes are located on autosomes, males and females are affected in roughly equal frequencies
The recurrence risk is thus 50%, so half the children will be affected - however if both parents are heterozygous, the recurrence risk is 75%, this is rare, and often more severe
Autosomal dominant pedigree characteristics
