Shane 3 (AI) Molecular Diagnostics - Whole Genoms/Whole Exome Sequencing Flashcards
What percentage of the human genome is similar across individuals?
99.9%
The differences in the human genome are only found in 0.1% of the genome.
What is the significance of genetic mutations in cancer?
Mutations are usually found in many different genes.
An example is the BRCA1 mutation, which often occurs alongside other mutations.
What is the relationship between mutations and cancer development?
Multiple mutations occur before someone develops cancer.
This indicates that cancer is often the result of cumulative genetic changes.
Define Mendelian disorders.
Mutations in one gene.
Examples include Cystic Fibrosis (CF) and Prader-Willi Syndrome (SNRPN gene).
What are some characteristics of Mendelian disorders?
Some remain mysterious with unknown causative genes.
This highlights gaps in current genetic understanding.
What is a method for prenatal diagnosis?
Cell-free fetal DNA from the mother.
This method is less invasive compared to traditional techniques.
What was previously used for prenatal diagnosis but is no longer commonly done?
Amniocentesis.
It was considered too risky for routine use.
Fill in the blank: Genetic mutations associated with cancer usually occur in _______.
[many different genes].
True or False: The majority of human genome differences are found in more than 0.1% of the genome.
False.
Differences are only in 0.1% of the genome.
What year did Watson and Crick infer DNA’s structure?
1953
What significant event in 1977 involved nucleotide sequencing?
The first nucleotide sequence of the gene encoding yeast alanine tRNA was reported
Who introduced initial DNA sequencing methods in 1980?
Sanger, Maxam, and Gilbert
What was the first human linkage map based on in 1983?
Restriction fragment length polymorphism
What significant discovery was made in 1985?
Mullis discovered the PCR technique
What idea was proposed in 1986?
The idea of human genome sequencing
What was cloned in 1990?
The first human disease gene
What was accomplished in 1993 regarding homozygosity?
The first homozygosity mapping was done
What was the focus of the first positional cloning done in 1995?
A recessive disease gene on the basis of linkage
What was reported in 1996 regarding genome sequencing?
The first genome sequence of an organism (Hemophilus influenza)
What major milestone occurred in 2001?
The first human chromosome was sequenced
What was the first organism whose genome was sequenced in 2000?
Fruit fly
In what year was the first draft of the human genome sequence published?
2001
What key event occurred in 2003 regarding the human genome?
The human genome sequence was completed
What technology emerged in 2005 that transformed sequencing?
Massively parallel sequencing platforms (next-generation sequencing)
What year saw the introduction of the first NGS instrument?
2009
What was the first application of WES reported in 2010?
Proof of principle: disease gene identification by WES
Fill in the blank: The PCR technique was discovered by _______.
Mullis
True or False: The first individual genome based on NGS was published in 2010.
True
What percentage of Watson’s genome was published in 2008?
33%
What major advancement in genetics was made in 1985?
PCR technique
Who received a Nobel Prize for the development of the PCR technique?
Mullis
What did Watson’s genome reveal about his health?
Predisposed to lots of conditions
What is the primary purpose of Whole Genome Sequencing?
To determine the complete DNA sequence of an organism’s genome
This includes identifying all of the organism’s genes and their functions.
What is a BAC in the context of genome sequencing?
Bacterial Artificial Chromosome
BACs are used to clone large fragments of DNA for genomic studies.
What is the first step in the Hierarchical Shotgun Approach?
Fragmenting genomic DNA into large pieces
This initial step allows for the organization and mapping of the genome.
What does the term ‘minimal tiling path’ refer to in genome sequencing?
The process of using restriction enzymes to digest DNA into smaller fragments
This approach helps to create a more manageable set of sequences for assembly.
Fill in the blank: In the shotgun approach, DNA is fragmented into different sizes like _______.
shotgun pellets
This metaphor illustrates the random nature of fragmenting DNA.
What is the significance of overlapping reads in genome assembly?
They allow for the reconstruction of the original sequence
Overlapping reads are crucial for accurate genome assembly.
True or False: The process of preparing chromosome spreads is simple and quick.
False
Preparing chromosome spreads is described as a tedious process.
What is the role of restriction enzymes in the shotgun sequencing process?
To cut DNA into fragments of varying sizes
This facilitates the cloning and sequencing of DNA.
What are shotgun clones made from?
BAC clones that have been digested into smaller fragments
Shotgun clones are the actual sequences that are read during sequencing.
What was a major reason why the Human Genome Project took approximately 10 years to complete?
The tedious process of assembling sequences from overlapping reads
The complexity of genome sequencing contributed to the lengthy timeline.
What does the term ‘reads’ refer to in the context of genome sequencing?
Short sequences of nucleotides obtained from shotgun clones
Reads are the data points used to assemble the genome.
What is the primary technique used in whole genome sequencing known as the shotgun approach?
The shotgun approach involves randomly breaking up DNA into smaller fragments and then sequencing those fragments to reconstruct the entire genome.
True or False: The shotgun sequencing method requires the genome to be assembled in a specific order before sequencing.
False
Fill in the blank: In shotgun sequencing, the DNA is first ______ into smaller fragments.
fragmented
Which of the following is a key advantage of the shotgun sequencing method? A) It is labor-intensive B) It requires prior knowledge of the genome C) It allows for rapid sequencing of large genomes
C) It allows for rapid sequencing of large genomes
