Genetics I

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

1. One diploid parent cell becomes 4 haploid daughter cells

• Crossing over occurs
• Gamete formation

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

<p>G1 → S → G2 → M</p> Signup and view all the answers

<p>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.</p> Signup and view all the answers

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

<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

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

<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

<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

<p>Single bases--&gt; DNA strand--&gt; whole chromosome</p> Signup and view all the answers

<p>All chromosomal material is present</p> Signup and view all the answers

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

<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

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

<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

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

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

<p>-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.</p> Signup and view all the answers

<p>Down's syndrome</p> Signup and view all the answers

<p>Spontaneous miscarriage</p> Signup and view all the answers

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

<p>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.</p> Signup and view all the answers

<p>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.</p> Signup and view all the answers

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

<p>No</p> Signup and view all the answers

<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

<p>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).</p> Signup and view all the answers

<p>Array CGH is the first line chromosome test. It is capable of finding polymorphisms.</p> <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

<p>Chromosome/ Karyotype analysis</p> Signup and view all the answers

<p>Amplifying, cloning and testing specific DNA sequences</p> Signup and view all the answers

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

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

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

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

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

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

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

<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

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

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

<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

<p>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.</p> Signup and view all the answers

<p>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.</p> Signup and view all the answers

<p>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.</p> Signup and view all the answers

<p>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.</p> Signup and view all the answers

<p>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</p> <ul> <li>Often used for finding specific features in DNA for use in genetic counselling</li> </ul> Signup and view all the answers

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

<p>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.</p> Signup and view all the answers

<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

<p>Reduced transcription or abnormal splicing, reduced protein</p> Signup and view all the answers

<p>If there's Exon 1, Exon 2 and Exon 3:-</p> <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

<p>Causes a complete change to the entire amino acid sequence after the mutation site</p> <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

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

<p>Point mutations that cause a change to a single amino acid.</p> <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

<p>Reference sequence; old base&gt; new base c.267 G&gt;A</p> Signup and view all the answers

<p>c.267delG</p> Signup and view all the answers

<p>c.267InsA Insertion of an A</p> Signup and view all the answers

<p>c.267+2T&gt;A</p> Signup and view all the answers

<p>p. Ile122Ile</p> Signup and view all the answers

<p>p. Ile122Val</p> Signup and view all the answers

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

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

<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

<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

<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

<p>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</p> Signup and view all the answers

<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

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

<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

<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

<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