Genetics I

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What is the structure of the DNA?

DNA strands pair up in an antiparallel fashion
Read and replicated 5’→3’
Sugar phosphate backbone (deoxyribose)
A + T, C + G
DNA strand associates with proteins (including histones) – wound into chromosomes

What is the role of meiosis in DNA replication?

One diploid parent cell becomes 4 haploid daughter cells

Crossing over occurs
Gamete formation

What is the yield from a process of mitosis?

One diploid parent cell gives rise to two identical diploid daughter cells

What are the steps in cell cycle?

G1 → S → G2 → M Signup and view all the answers

How do disease occur through the process of DNA replication?

DNA replication happens during the S phase. DNA can be damaged during replication. There are repair mechanisms and when there are defects in it, it causes disease. Signup and view all the answers

What is the structure of the RNA?

<ul> <li>Single stranded</li> <li>Ribose sugar backbone</li> <li>U replaces T</li> </ul> Signup and view all the answers

What are the determining factors for the amount of protein produced?

<ol> <li>Rate of transcription (manufacture of pre-mRNA</li> <li>Rate of splicing to mRNA</li> <li>Half life of mRNA</li> <li>Rate of processing of polypeptide (modification) and movement around the cell.</li> </ol> Signup and view all the answers

What are the sequence variations within a gene?

<ul> <li>Changes in promoter sequence</li> <li>Changes in exon sequence</li> </ul> Signup and view all the answers

What are the sequence changes in the DNA between the genes?

<ol> <li>SNPs: Single Nucleotide Polymorphisms <ul> <li>Affect gene function, some effects may make you more prone to disease e.g. by affecting transcription (alter promoter)</li> <li>Most have no effect</li> </ul> </li> <li>CVNs (copy number variation): extra/missing stretches of DNA; deletions or duplications <ul> <li>Number of copies of a particular gene varies from one individual to the next</li> </ul> </li> </ol> Signup and view all the answers

How does variation occur through meiosis and mitosis?

<ol> <li>Meiosis causes variation because it involves chromosomes crossing over and DNA recombination.</li> <li>Mitosis is supposed to produce identical daughter cells but DNA replication is imperfect and the cells acquire mutations through mitosis.</li> </ol> Signup and view all the answers

What is the genomic structure from least to most complex?

Single bases--> DNA strand--> whole chromosome Signup and view all the answers

What is a balanced chromosome rearrangement?

All chromosomal material is present Signup and view all the answers

What is an unbalanced chromosome rearrangement? What is its impact?

Extra or missing chromosomal material, usually 1 or 3 copies of gene. It causes major developmental problems. Signup and view all the answers

What is aneuploidy?

<ul> <li>Whole extra or missing chromosome</li> <li>X chromosome aneuploidy better tolerated because of X chromosome inactivation (one X chromosome gets inactivated in embryonic development to only have 1 copy)</li> </ul> Signup and view all the answers

What is chromosomal translocation?

A translocation, as related to genetics, occurs when a chromosome breaks and the (typically two) fragmented pieces re-attach to different chromosomes. Signup and view all the answers

What is Robertsonian translocation?

<ul> <li>Two acrocentric chromosomes stuck end to end</li> <li>Increased risk of trisomy in pregnancy</li> </ul> Signup and view all the answers

What is reciprocal translocation?

Two broken off chromosome pieces of non-homologous chromosomes are exchanged Signup and view all the answers

What is the difference between crossing over in meiosis and reciprocal translocation in genetics?

Crossing over occurs between paired homologous chromosomes while reciprocal translocation is exchange of DNA material in non-homologous chromosomes. Signup and view all the answers

What is the difference between a balanced and unbalanced translocation?

-A balanced translocation involves an even exchange with no genetic material added or substracted (ideally with normal function as a result). -An unbalanced translocation results in either missing or extra DNA and results in an abnormal gene. Signup and view all the answers

What condition does this karyotype correspond to- 47 XY +21 (Trisomy 21)?

Down's syndrome Signup and view all the answers

What condition does this karyotype correspond to- 47 XY +14 (trisomy 14)?

Spontaneous miscarriage Signup and view all the answers

What condition does this karyotype correspond to- 47 XY +18 (trisomy 18)?

Edward Syndrome (decreased muscle symptoms, affects cognitive and internal organ development) Signup and view all the answers

What condition does this karyotype correspond to- 45 XY?

Turner syndrome (a short neck with a webbed appearance, low hairline at the back of the neck, low-set ears, swollen hands or feet and soft nails that turn upward. Signup and view all the answers

What condition does this karyotype correspond to- 47 XXY?

Klinefelter syndrome (a taller, less muscular body, broader hips and longer legs and arms, larger breasts (a condition called gynecomastia), weaker bones, a lower energy level, smaller penis and testicles. Signup and view all the answers

What is somatic mosaicism?

It refers to the occurrence of two genetically distinct populations of cells within an individual, derived from a post-zygotic mutation. Signup and view all the answers

Is somatic mosaicism transferred to progeny?

No Signup and view all the answers

How can somatic mosaicism contribute to cancer?

<ul> <li>Somatic mosaicism for a chromosomal abnormality could contribute to cancer <ul> <li>Changes could activate an oncogene or delete a tumour suppressor</li> </ul> </li> </ul> Signup and view all the answers

What is the difference between germline and somatic mosaicism?

Germline mosaicism is a mutation that is limited to the gonads and can be transmitted to offspring. Somatic mosaicism is a postzygotic mutation that occurs in the soma, and it may occur at any developmental stage or in adult tissues (spontaneously). Signup and view all the answers

What is Array CGH?

Array CGH is the first line chromosome test. It is capable of finding polymorphisms. <ol> <li>It can detect any size of imbalance (unbalanced rearrangements).</li> <li>It does not detect balanced rearrangements</li> </ol> Signup and view all the answers

What test would be appropriate for balanced chromosomal rearrangements?

Chromosome/ Karyotype analysis Signup and view all the answers

What is the function of the PCR (Polymerase chain testing)?

Amplifying, cloning and testing specific DNA sequences Signup and view all the answers

What is a mutation?

Any heritable change in the human genome which causes a genetic disorder Signup and view all the answers

What is a polymorphism?

Any variation in human genome which has a population frequency >1% - Does not cause disease in its own right, but may predispose to common disease Signup and view all the answers

What is penetrance?

The likelihood of having a disease if you have a gene mutation Signup and view all the answers

What is a Mendelian disorder (classical genetic disease)?

One mutation sufficient to cause disease - High penetrance, small environmental contribution Signup and view all the answers

What is a multifactorial disease?

Multiple polymorphisms cause a risk of disease - Penetrance for any one mutation is low Signup and view all the answers

What are exons?

Exons are the coding regions of a gene. They are the segments of DNA that are transcribed into mRNA and eventually translated into protein. Signup and view all the answers

What are the functions of exons?

Exons contain the information necessary for synthesizing functional proteins. They contribute to the final mRNA that is processed and translated during protein synthesis. Signup and view all the answers

What are the characteristics of exons?

<ol> <li>Exons are typically continuous coding sequences.</li> <li>They often correspond to functional domains or specific regions of the protein product.</li> <li>Exons are retained in the mature mRNA after the removal of introns during RNA processing.</li> </ol> Signup and view all the answers

What are introns?

Introns are non-coding regions of a gene. They are intervening sequences that are transcribed into pre-mRNA but are not translated into protein. Signup and view all the answers

What are the functions of introns?

The exact function of introns is not fully understood, but they play crucial roles in gene regulation, alternative splicing, and other cellular processes. Signup and view all the answers

What are the characteristics of introns?

<ol> <li>Introns may be quite long and are often rich in repetitive sequences.</li> <li>They are transcribed along with exons to form the pre-mRNA.</li> <li>During RNA processing (specifically, splicing), introns are removed, and exons are ligated together to form the mature mRNA.</li> </ol> Signup and view all the answers

What is splicing?

The process of removing introns and joining exons to form the mature mRNA is called splicing. This process is essential for generating a functional mRNA transcript for translation. Signup and view all the answers

What is alternative splicing?

Some genes can undergo alternative splicing, where different combinations of exons are included or excluded in the final mRNA. This can result in multiple protein isoforms from a single gene. Signup and view all the answers

What is the difference between the genomic DNA and complementary DNA (cDNA)?

When comparing the DNA sequence of a gene in the genome (genomic DNA) to the complementary DNA sequence generated from mature mRNA (cDNA), introns are absent in the cDNA sequence because they are spliced out during RNA processing. Signup and view all the answers

What is a promoter?

The promoter is a region of DNA upstream of a gene where relevant proteins (such as RNA polymerase and transcription factors) bind to initiate transcription of that gene. e.g. TATA box is a promoter sequence. Signup and view all the answers

What is the FISH test? What is it used for?

FISH or (Fluorescence in-situ Hybridisation) uses fluorescent probes that bind only to parts of a nucleic acid sequence with a high degree of sequence complementarity <ul> <li>Often used for finding specific features in DNA for use in genetic counselling</li> </ul> Signup and view all the answers

What is whole exome sequencing? How is it different from genome sequencing?

Sequences exome - all the exons (vs. whole genome sequencing – introns and exons) Signup and view all the answers

What is genetic filtering?

To identify the pathogenic variant, the list of variants is filtered to remove those that are unlikely to be disease causing. -On average approx. 3 000 000 polymorphisms are detected when sequencing the entire genome in a person. It can be narrowed down to a mutation. Signup and view all the answers

How do you narrow down a variant in genetic filtering?

<ol> <li>3 million genetic variants (exclude if it is known to be a polymorphism)</li> <li>1000s of genetic variants (keep if it affects gene function (stop, splice etc.)</li> <li>100s of genetic variants (is it in a gene that explains the phenotype?)</li> <li>1 or a few mutations (ideally)</li> </ol> Signup and view all the answers

What effect does promotor mutation have?

Reduced transcription or abnormal splicing, reduced protein Signup and view all the answers

What effect does change in amino acid sequence have through altered splicing?

If there's Exon 1, Exon 2 and Exon 3:- <ol> <li>Exon 1/ Exon 3/ Stop- makes an abnormal or absent protein</li> <li>Exon 1/ Exon 2/ Stop- makes a short or absent protein- premature stop codon It causes the formation of different or non-functioning protein.</li> </ol> Signup and view all the answers

What is the effect of insertion/ deletion within an amino acid sequence? What are two types of mutations in this?

Causes a complete change to the entire amino acid sequence after the mutation site <ol> <li>In frame - insertion/deletion of a multiple of 3 bases</li> <li>Out of frame - results in a frame shift</li> </ol> Signup and view all the answers

What are the stop codons in the DNA sense (coding) strand and the mRNA?

<ol> <li>Sense strand- TAA, TAG, TGA</li> <li>mRNA- UAA, UAG, UGA</li> </ol> Signup and view all the answers

What is a missense mutation?

Point mutations that cause a change to a single amino acid. <ul> <li>Usually caused by substitutions (CAG to AAG for example)</li> <li>Most likely mutation to directly activate an oncogene</li> <li>Other mutations tend to inactivate the gene</li> </ul> Signup and view all the answers

What is the nomenclature of substitution mutation on the mRNA (cDNA) sequence?

Reference sequence; old base> new base c.267 G>A Signup and view all the answers

What is the nomenclature of deletion mutation on the mRNA (cDNA) sequence?

c.267delG Signup and view all the answers

What is the nomenclature of insertion mutation on the mRNA (cDNA) sequence?

c.267InsA Insertion of an A Signup and view all the answers

What is the nomenclature of substitution mutation on the mRNA (cDNA) sequence?

c.267+2T>A Signup and view all the answers

What is the nomenclature of no effect mutation on the peptide sequence?

p. Ile122Ile Signup and view all the answers

What is the nomenclature of missense mutation on the peptide sequence?

p. Ile122Val Signup and view all the answers

What is the nomenclature of premature stop/ nonsense mutation on the peptide sequence?

p. Ile122Ter or p.Ile122* Signup and view all the answers

What is the nomenclature of deletion mutation on the peptide sequence?

p. Ile122Thr fs <ul> <li>This is where deletion causes Ice to The and Frameshift mutation.</li> </ul> Signup and view all the answers

What are the characteristics of autosomal mode of inheritance?

<ol> <li>Only one copy required to cause disease</li> <li>Disease seen in all generations.</li> </ol> <ul> <li>A person affected by an autosomal dominant disorder has a 50% chance of passing the mutated gene to each child</li> </ul> Signup and view all the answers

What is the autosomal dominant mode of inheritance?

<ol> <li>Only one copy required to cause disease</li> <li>Disease seen in all generations.</li> </ol> <ul> <li>A person affected by an autosomal dominant disorder has a 50% chance of passing the mutated gene to each child</li> </ul> Signup and view all the answers

What is the autosomal recessive mode of inheritance?

<ol> <li>2 copies of faulty gene required to cause disease</li> <li>Often only 1 generation affected</li> </ol> <ul> <li>1 in 4 risk of child being affected if parents are carriers</li> </ul> Signup and view all the answers

What is X linked inheritance?

A female with one pathogenic allele and one normal allele does not show major clinical features of the disease, but a male with a single faulty allele will be fully affected. Gene fault lies on the X chromosome Signup and view all the answers

What are the inheritable characteristics of X linked inheritance in males and females?

<ol> <li>Carrier female may have an unaffected son (1/4), affected son (1/4), unaffected daughter (1/4), carrier daughter (1/4)</li> <li>If an affected male has children, all his daughters will be carriers and all his sons will be unaffected (no male-male transmission)</li> </ol> Signup and view all the answers

Does a female carrier in X linked inheritance show any features of the condition and why?

Female carrier may show mild features – X inactivation (around ½ of cells will have faulty gene) Signup and view all the answers

What is mitochondrial inheritance?

<ol> <li>The mitochondria in the cell have their own genome (single loop)</li> <li>In many cases, a mutation in the mitochondrial genome is only present in a proportion of the mitochondria, and the proportion varies between cells within an individual</li> <li>Mitochondrial DNA is transmitted maternally, in the ovum</li> </ol> Signup and view all the answers

How does genetic mutation cause disease?

<ul> <li>Haploinsufficiency: only one copy of working gene, reduced protein production</li> <li>Dominant negative: expression of abnormal protein interferes with normal protein</li> <li>Gain of function: mutant protein gains a new function, affecting cell processes</li> <li>Complete loss of function: autosomal recessive, 2 copies of faulty gene produces no protein</li> </ul> Signup and view all the answers

What is precision medicine and what is it used for?

<ul> <li>Use some form of testing (genetic testing, understanding molecular pathways) to identify a subgroup of patients who respond to treatment</li> <li>Most effective for rare diseases and high penetrance mutations</li> </ul> Signup and view all the answers

Genetics I

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Questions and Answers

What is the structure of the DNA?

What is the role of meiosis in DNA replication?

What is the yield from a process of mitosis?

What are the steps in cell cycle?

How do disease occur through the process of DNA replication?

What is the structure of the RNA?

What are the determining factors for the amount of protein produced?

What are the sequence variations within a gene?

What are the sequence changes in the DNA between the genes?

How does variation occur through meiosis and mitosis?

What is the genomic structure from least to most complex?

What is a balanced chromosome rearrangement?

What is an unbalanced chromosome rearrangement? What is its impact?

What is aneuploidy?

What is chromosomal translocation?

What is Robertsonian translocation?

What is reciprocal translocation?

What is the difference between crossing over in meiosis and reciprocal translocation in genetics?

What is the difference between a balanced and unbalanced translocation?

What condition does this karyotype correspond to- 47 XY +21 (Trisomy 21)?

What condition does this karyotype correspond to- 47 XY +14 (trisomy 14)?

What condition does this karyotype correspond to- 47 XY +18 (trisomy 18)?

What condition does this karyotype correspond to- 45 XY?

What condition does this karyotype correspond to- 47 XXY?

What is somatic mosaicism?

Is somatic mosaicism transferred to progeny?

How can somatic mosaicism contribute to cancer?

What is the difference between germline and somatic mosaicism?

What is Array CGH?

What test would be appropriate for balanced chromosomal rearrangements?

What is the function of the PCR (Polymerase chain testing)?

What is a mutation?

What is a polymorphism?

What is penetrance?

What is a Mendelian disorder (classical genetic disease)?

What is a multifactorial disease?

What are exons?

What are the functions of exons?

What are the characteristics of exons?

What are introns?

What are the functions of introns?

What are the characteristics of introns?

What is splicing?

What is alternative splicing?

What is the difference between the genomic DNA and complementary DNA (cDNA)?

What is a promoter?

What is the FISH test? What is it used for?

What is whole exome sequencing? How is it different from genome sequencing?

What is genetic filtering?

How do you narrow down a variant in genetic filtering?

What effect does promotor mutation have?

What effect does change in amino acid sequence have through altered splicing?

What is the effect of insertion/ deletion within an amino acid sequence? What are two types of mutations in this?

What are the stop codons in the DNA sense (coding) strand and the mRNA?

What is a missense mutation?

What is the nomenclature of substitution mutation on the mRNA (cDNA) sequence?

What is the nomenclature of deletion mutation on the mRNA (cDNA) sequence?

What is the nomenclature of insertion mutation on the mRNA (cDNA) sequence?

What is the nomenclature of substitution mutation on the mRNA (cDNA) sequence?

What is the nomenclature of no effect mutation on the peptide sequence?

What is the nomenclature of missense mutation on the peptide sequence?

What is the nomenclature of premature stop/ nonsense mutation on the peptide sequence?

What is the nomenclature of deletion mutation on the peptide sequence?

What are the characteristics of autosomal mode of inheritance?

What is the autosomal dominant mode of inheritance?

What is the autosomal recessive mode of inheritance?

What is X linked inheritance?

What are the inheritable characteristics of X linked inheritance in males and females?

Does a female carrier in X linked inheritance show any features of the condition and why?

What is mitochondrial inheritance?

How does genetic mutation cause disease?

What is precision medicine and what is it used for?

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