Foundations of medicine Block 1 Week 2 Flashcards

Question

What is Euchromatin ?

Answer 1

- 'unpacked' beads on a string - is a lightly packed form of chromatin (DNA, RNA, and protein) that is enriched in genes, and is often (but not always) under active transcription.

Answer 2

- 'Packed' 30nm fibres. - Adjacent nucleosomes packed together to form a chromatin fibre of 30nm diameter.

Answer 3

1. 46 chromosomes

Answer 4

homologous chromosome pairs

Answer 5

1. During metapahse chromosomes are visible as duplicated chromatids attached at the centreomere.

Answer 6

The cell cycle is an ordered series of events that leads to division of a cell into two identical daughter cells. The duration of a cell cycle depends on the cell type. In a fast dividing cell it is approx 24 hrs.

Answer 7

Female: 46, XX Male: 46, XY

Answer 8

Trisomy 21 is also known as Downs syndrome Female karyotype: 47, XX, +21 Male karyotype: 47, XY, +21

Answer 9

Mitosis is when the cell divides.

Answer 10

the cytoplasmic division of a cell at the end of mitosis or meiosis, bringing about the separation into two daughter cells.

Answer 11

G0 phase (resting stage): The cell has not yet started to divide. Cells spend much of their lives in this phase. Depending on the type of cell, G0 can last from a few hours to a few years. When the cell gets a signal to divide, it moves into the G1 phase. G1 phase (interphase): During this phase, the cell starts making more proteins and growing larger, so the new cells will be of normal size. This phase lasts about 18 to 30 hours. S phase (interphase): In the S phase, the chromosomes containing DNA are copied so that both of the new cells formed will have matching strands of DNA. The S phase lasts about 18 to 20 hours. G2 phase (interphase): In the G2 phase, the cell checks the DNA and gets ready to start splitting into 2 cells. This phase lasts from 2 to 10 hours. M phase (mitosis): In this phase, which lasts only 30 to 60 minutes, the cell actually splits into 2 new cells. Cytokinesis - the cytoplasm splits There are checkpoints to make sure the cell cycle is happening correctly. These happen at different points. Metaphase checkpoint. G1 checkpoint. G2 checkpoint (G=gap, S=synthesis, M=mitosis)

Answer 12

Prophase: Chromosome condensation Dispersal of nucleoli Separation of centrosomes and formation of mitotic spindle Prometaphase: Fragmentation of the nuclear envelope Attachment of spindle MTs to centromeres Chromosomes start to move towards cell centre (congression)

Answer 13

Metaphase 1.Chromosome alignment at metaphase plate Anaphase: Chromosomes (chromatids) move to opposite cell poles Telophase: Chromosomes uncoil Nucleoli develop and fuse Disassembly of spindle Re-formation of the nuclear envelope

Answer 14

The mitotic spindle is formed from microtubules and is organised from the two centromeres which migrate to the opposite poles during mitosis. The microtubules attach to the centromere of chromosomes via the kinetochore.

Answer 15

Fluorouracil, which is often called 5FU, is a chemotherapy therapy drug used to treat different cancers including breast, bowel, skin, stomach, oesophageal (gullet), and pancreatic cancer. Brand name: Adrucil

Answer 16

A unit of heredity that is transferred from a parent to the offspring and is held to determine some characteristic of the offspring

Answer 17

Detection of Creatine Kinase in circulation is a highly sensitive diagnostic marker of myocardial infarction (better than ECG

Answer 18

- 2% of our genes make proteins - Genes that code for a protein are called protein - coding gene. A protein coding gene contains all the nucleotide sequence necessary to produce a mature messenger RNA (mRNA).

Answer 19

- Nearly half of our genome is actively used ( transcribed ) in the form of non-protein -coding RNA.

Answer 20

When and where a gene is transcribed is under the control of the promoter and regulatory sequences of the gene. A gene is transcribed by RNA polymerase. Proteins called “transcription factors” bind to the promoter and regulatory sequences of the gene and influence gene transcription. The combination of transcription factors bound to the promoter and regulatory sequences modulates the activity of RNA polymerase and determines where, when and at what levels a gene is transcribed.

Answer 21

The exons and introns constitute the parts of a gene that are transcribed. Both exons and introns constitute the immature pre-mRNA. During the maturation of the pre-mRNA to form a mature mRNA the intron sequences form a loop structure and are excised in association with a complex called the spliceosome. This is called splicing. The protein coding region is contained within the exons.

Answer 22

In addition to splicing the primary transcript is modified at its 5’ and 3 ends’. These modifications are important for efficient translation and stabilisation of the message Capping: A cap structure (7-methyl guanosine) is added to the 5’ end of mRNAs shortly after transcription is initiated. Polyadenylation: At the 3’ end of the RNA the enzyme poly-A polymerase adds 100 to 300 Adenine residues to form a poly-A tail.

Answer 23

The levels of mature mRNA are further regulated after transcription and before translation by non-coding RNAs. Examples include microRNAs, long non-coding RNA microRNAs reduce levels of mRNAs by destabilising them and inhibiting initiation of their translation. The effect of microRNAs on mRNAs is called RNA-induced silencing.

Answer 24

- The transformation of genetic information (bases) into proteins (amino acid sequences) is based on the genetic code. -The coding region of an mRNA is read in triplets of bases known as codons. Each codon corresponds to an amino acid or a translation stop signal (stop codon). -The genetic code is a degenerate code. There are only 20 amino acids and three stop codons. Most amino acids are coded for by more than one codon. - Knowing the nucleotide sequence of an mRNA allows us to derive the amino acid sequence of its protein product. -The formation of the peptide chain is catalysed and orchestrated by ribosomes in the cytoplasm. -Ribosomes associate with a number of regulatory proteins, including initiating and releasing factors. -The sequence of codons from the AUG (initiator – methionine) to the terminating stop codon is known as the open reading frame or ORF.

Answer 25

-Ribosomes are high molecular weight structures composed of protein and RNA. -Ribosomes are composed of two sub-units. -The small ribosomal sub-unit binds tRNA and mRNA. -The large ribosomal sub-unit catalyzes the addition of amino acids to the extending peptide chain.

Answer 26

Translation is initiated at an AUG codon which codes for the amino acid methionine Small ribosomal sub-unit scans along mRNA from 5’ end The small and large ribosomal sub-units assemble at the initiator and begin to translate the mRNA into protein AUG - AND U GO

Answer 27

Many antibiotics are inhibitors of bacterial protein synthesis. Antibiotics make use of the structural and functional differences between eukaryotic and prokaryotic ribosomes Tetracycline blocks entry of tRNAs into ribosome complex. Chloramphenicol blocks addition of new amino acids into peptide chain. Tetracycline is used to treat infections caused by bacteria including pneumonia and other respiratory tract infections; ; certain infections of skin, eye, lymphatic, intestinal, genital and urinary systems; and certain other infections that are spread by ticks, lice, mites, and infected animals. Chloramphenicol is a broad spectrum antibiotic that is effective against a variety of susceptible and serious bacterial infections but is not frequently used because of its high risk of bone marrow toxicity.

Answer 28

Following translation proteins are further modified and acquire three dimensional structures. Common post-translational modifications include glycosylation (addition of sugar residues) and phosphorylation (addition of phosphate groups). Misfolded proteins are ubiquitinated (addition of a small chemical moiety called ubiquitin) and degraded. The function and localisation of proteins in a cell is determined by their structure and post-translational modification.

Answer 29

The localisation of a protein in a cell is determined by its structure and post-translational modifications. Many proteins that are found in the nucleus contain a nuclear localisation signal peptide in their sequence. In other cases only the phosphorylated form of a protein can be transported to the nucleus. Proteins that are either secreted from the cell or are inserted into cellular plasma membrane have an endoplasmic reticulum (ER) signal sequence or peptide at their amino terminus. Membrane associated and secreted proteins which have passed into the ER are trafficked in vesicles to the Golgi apparatus, where they are further modified.

Answer 30

Metacentric chromosome (1): Centomere is in the centre p and q arms are equal in length eg chromosome 1 Submetacentric chromosomes (4): Centomere is slightly offset from the centre eg chromosome 4 Acrocentric chromosome (13) : Centomere is severely offset from the centre p arm is very short eg chromosome 13

Answer 31

This is called Chromosome (metaphase) spread. Chromosomes are visible during metaphase of cell division Arrest the cells in metaphase by treatment with colcemid, which disrupts the cell spindle Fix and drop the cell suspension onto a microscope slide

Answer 32

Giemsa staining of chromosomes (G banding) Laboratory protocols result in dark and light banding patterns Dark bands correspond to condensed A, T rich (gene poor) regions of the chromosomes. G-banding, G banding or Giemsa banding is a technique used in cytogenetics to produce a visible karyotype by staining condensed chromosomes. It is the most common chromosome banding method. It is useful for identifying genetic diseases through the photographic representation of the entire chromosome complement.The metaphase chromosomes are treated with trypsin (to partially digest the chromosome) and stained with Giemsa stain. Heterochromatic regions, which tend to be rich with adenine and thymine (AT-rich) DNA and relatively gene-poor, stain more darkly in G-banding. In contrast, less condensed chromatin (Euchromatin)—which tends to be rich with guanine and cytosine (GC-rich) and more transcriptionally active—incorporates less Giemsa stain, and these regions appear as light bands in G-banding. The pattern of bands are numbered on each arm of the chromosome from the centromere to the telomere. This numbering system allows any band on the chromosome to be identified and described precisely.

Answer 33

Locus: In genetics, a locus is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. A gene is said to be polymorphic if more than one allele occupies that gene's locus within a population. In addition to having more than one allele at a specific locus, each allele must also occur in the population at a rate of at least 1% to generally be considered polymorphic. The majority of polymorphisms are silent, meaning they do not alter the functionGene allele can have two or more variants Most genes are ‘polymorphic’ Variants can be classified as common (population frequency ≥1%) or rare (population frequency <1%) Geographical differences in allele frequency or expression of a gene.[3] Some polymorphisms are visible. For example, in dogs the E locus can have any of five different alleles, known as E, Em, Eg, Eh, and e.[4] Varying combinations of these alleles contribute to the pigmentation and patterns seen in dog coats.

Answer 34

Microsatellite, as related to genomics, refers to a short segment of DNA, usually one to six or more base pairs in length, that is repeated multiple times in succession at a particular genomic location. These DNA sequences are typically non-coding.

Answer 35

Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction

Answer 36

Homozygous e.g ( alleles B2 and B2)

Answer 37

Heterozygous e.g. (alleles A7 and A9)

Answer 38

Occur throughout an individual’s DNA sequence Commonly found in non-coding DNA but can occur in exons Approximately 1 SNV per 1000 nucleotides (4-5 million SNV per individual’s genome) A DNA sequence variation that occurs when a single nucleotide (adenine, thymine, cytosine, or guanine) in the genome sequence is altered. Single nucleotide variants may be rare or common in a population

Answer 39

The polymerase chain reaction is a method widely used to rapidly make millions to billions of copies of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it to a large enough amount to study in detail. Polymerase chain reaction (PCR) generates millions of copies of a specific DNA sequence in a few hours PCR can be used on minute amounts of starting DNA Widely used to generate sufficient DNA prior to detection & identification of DNA variants

Answer 40

Short tandem repeats ( STR) Single nucleotide variants ( SNV) Polymorphism, as related to genomics, refers to the presence of two or more variant forms of a specific DNA sequence that can occur among different individuals or populations. The most common type of polymorphism involves variation at a single nucleotide

Answer 41

Simple repeated DNA sequence motifs (also known as microsatellites) ‘Length polymorphisms’, e.g. dinucleotide: (CA)(CA)(CA)(CA)(CA)(CA) trinucleotide: (GCC)(GCC)(GCC)(GCC)(GCC) tetranucleotide: (AATG)(AATG)(AATG)(AATG) Many possible alleles (highly ‘polymorphic’) Genome wide, but mostly located in non-coding regions

Answer 42

- To see the risk for the individual - Risk of developing the disease -Risk of being a carrier of the disease Family history helps determine this

Answer 43

Prevention Genetic counselling Risk for other family members Risk for unborn child Preventative surgery and treatment

Answer 44

Adaption and evolution Natural selection (gene pool)

Answer 45

Exopnential amplification x35-40

Answer 46

Microsatellites

Answer 47

A9 - allele with 9 repeats A7 - allele with 7 repeats

Answer 48

Because of genetic redundancy. Many amino acids have 3 triplets that give rise to the same amino acid. So a change in the codon may not result in a chanage in the amino acid. Even if a change did happen. This change be insignigicant and may not ahve a bif impact on that protein.

Answer 49

first type of SNV and also acts as a recognition site for restriction enzyme Restriction fragment length polymorphism (abbreviated RFLP) refers to differences (or variations) among people in their DNA sequences at sites recognized by restriction enzymes. Such variation results in different sized (or length) DNA fragments produced by digesting the DNA with a restriction enzyme. RFLPs can be used as genetic markers, which are often used to follow the inheritance of DNA through families.

Answer 50

Introns - non coding regions Exons - coding regions Pre-mRNA contains introns and exons. Splicing happens after this has occured. Splicing coverts pre-mRNA into functional mRNA.

Answer 51

It means more than one triplet can code for the same amino acid. Infact most amino acids can be coded by 4 triplets.

Answer 52

The same codons will code for the same amino acids across all organisms.

Answer 53

AUG which codes for methionine

Answer 54

UAA UAG UGA

Answer 55

Banding patterns are patterns of light and dark transverse bands on chromosomes. The light and dark bands become apparent by staining the chromosome with a chemical solution and then viewed under a microscope. These bands describe the location of genes on a chromosome. Identification of chromosomes: - Chromosome length - Chromosome structure ( centromere location, p - arm, q -arm) - Normal banding pattern of each chromosome. Light bands represent early replicating regions, rich in guanine and cytosine nucleotides. Dark bands represent late replicating regions, rich in adenine and thymine nucleotides.

Answer 56

The pattern of bands are numbered on each arm of the chromosome from the centromere to the telomere. This numbering system allows any band on the chromosome to be identified and described precisely. The reverse of G‑bands is obtained in R‑banding. Banding can be used to identify chromosomal abnormalities, such as translocations, because there is a unique pattern of light and dark bands for each chromosome.

Answer 57

- Duplication - Inversion - Deletion - Insertion - Translocation

Answer 58

Males are born with extra X chromosome. 47, XXY Sex chromosome abnormality Numerical abnormality Klinefelter syndrome (sometimes called Klinefelter's, KS or XXY) is where boys and men are born with an extra X chromosome. Klinefelter syndrome may adversely affect testicular growth, resulting in smaller than normal testicles, which can lead to lower production of testosterone. The syndrome may also cause reduced muscle mass, reduced body and facial hair, and enlarged breast tissue. The effects of Klinefelter syndrome vary, and not everyone has the same signs and symptoms. Most men with Klinefelter syndrome produce little or no sperm, but assisted reproductive procedures may make it possible for some men with Klinefelter syndrome to father children.

Answer 59

Turner syndrome, a condition that affects only females, results when one of the X chromosomes (sex chromosomes) is missing or partially missing. - Numerical abnormality - Sex chromosome abnormality - Monosomy X - 45, X In childhood, teens and adulthood The most common signs in almost all girls, teenagers and young women with Turner syndrome are short stature and ovarian insufficiency due to ovarian failure. Failure of the ovaries to develop may occur at birth or gradually during childhood, the teen years or young adulthood. Signs and symptoms of these include: Slowed growth No growth spurts at expected times in childhood Adult height significantly less than might be expected for a female member of the family Failure to begin sexual changes expected during puberty Sexual development that "stalls" during teenage years Early end to menstrual cycles not due to pregnancy For most females with Turner syndrome, inability to conceive a child without fertility treatment

Answer 60

- Numerical abnormality - 47, XX, +21 - 47, XY, +21 - Also known as Trisomy 21 - Autosome abnormality - Increased risk with maternal age. - Prenatal diagnosis

Answer 61

Down syndrome screening by NIPT NIPT is a blood test that is more accurate than the first pregnancy screening test. It's offered to women who are carrying a baby identified from previous screening tests as having a higher chance of having either Down's syndrome, Edwards' syndrome, or Patau's syndrome. No screening test is 100% accurate.

Answer 62

Down syndrome screening by NIPT NIPT is a blood test that is more accurate than the first pregnancy screening test. It's offered to women who are carrying a baby identified from previous screening tests as having a higher chance of having either Down's syndrome, Edwards' syndrome, or Patau's syndrome. No screening test is 100% accurate.

Answer 63

- Egg ( 23 chromosomes) (haploid) - Sperm ( 23 chromosomes ) ( haploid ) - Zygote ( 46 chromosomes ) ( diploid)

Answer 64

Triple bases know as codons code for specific amino acids. Amino acids join together to make a specific protein. If there is a non-functional amino acid in the protein it is possible it could stop that protein form functioning correctly if at all. It is possible that the amino acid that was coded wrong was degenerate. Often one amino acid can be coded for by more than one triplet. So it could be that the change in bases did not change the amino acid in that protein chain.

Answer 65

Base substitutions - (substituting once base for another). Only a single nucleotide (base) is changed so one codon is affected. Although a base substitution only alters a single codon in a gene, it can have a significant effect on protein production. Base substitutions can lead to 3 subcategories of mutation. Missense mutations: in which altered codon leads to the insertion of an incorrect amino acid into a protein molecule during translation. Nonsense mutation: Altered codon prematurely terminates synthesis of a protein molecule. Silent mutation: altered codon codes for the same amino acid as unaltered codon.

Answer 66

- FEC ( Fluorouracil (5FU), Epirubicin, Cyclophosphamide) for breast colon and other cancers. - Methotrexate for various cancers ( and autoimmune diseases) - Vinblastine and paclitaxel for various cancers including breast. 5FU: inhibits thymidylate synthase, methotrexate inhibits dihydrofolate reductase; interfere with DNA replication by blocking synthesis of thymine. Cyclophosphamide: alkylating agent. Alkylates guanine, causes DNA crosslinks, interferes with DNA replication. Highly toxic and theratogenic. Epirubicin: intercalating agent, blocks replication and transcription, damages DNA

Answer 67

- Cyclophosphamide for synthetic lupus erythematosus Cyclophosphamide: alkylating agent. Alkylates guanine, causes DNA crosslinks, interferes with DNA replication. Highly toxic and theratogenic.

Answer 68

Cyclosporin Tacrolimus Sirolimus during renal trasnplantation. Cyclosporin: binds cyclophilin, inhibits calcineurin; complex signalling that blocks transcription of certain genes and lowers activity of T-cells Tacrolimus, sirolimus: inhibit calcineurin; complex signalling that blocks transcription of certain genes and lowers activity of T-cells (Calcineurin is a calcium-binding protein; calcium necessary to activate T cells)

Answer 69

- RNA polymerase makes an RNA copy of the sense DNA strand using the antisense DNA strand as the template. RNA polymerase moves along the template in a 3’ to 5’ direction and adds nucleotides to the 3’ end of the growing RNA chain (the RNA grows 5’ to 3’).

Answer 70

The most common type of DNA profiling today for criminal cases and other types of forensic uses is called "STR" (short tandem repeat) analysis. Using DNA to distinguish between two individuals is a tricky matter, because close to 99.9 percent of our DNA is the same as everybody else's DNA. Analysis of DNA length Many alleles (e.g. 1-8) per STR (highly ‘polymorphic’) Current laboratory methods can analyse multiple STR simultaneously Provide an unique pattern (fingerprint) for forensics, paternity testing, etc. Short tandem repeats (STRs) are short repeated sequences of DNA (2–6 bp) that account for approximately 3% of the human genome (Lander et al., 2001). The number of repeat units is highly variable among individuals, which offers a high power of discrimination when analyzed for identification purposes

Answer 71

Restriction fragment length polymorphism (RFLP) is used to detect sickle cell disease based on restriction enzymes, which remove the recognition site at the βs mutated gene

Answer 72

1. AA 2. AS 3. SS

Answer 73

Arises via recombination during meiosis

Answer 74

Its the DNA sequence of the entire human genome. Completed in 2003 and identified approx. 30,000 human genes. Has enabled the study of gene function, disease - associated genes and 'polymorphisms' / mutations.

Answer 75

The Hardy-Weinberg equation is a mathematical equation that can be used to calculate the genetic variation of a population at equilibrium. The Hardy - Weinberg principle is a mathematical model which can be used to predict the allele frequencies within a population. p2 + 2pq + q2 = 1 p2 = dominant homozygous frequency (AA) 2pq = heterozygous frequency (Aa) q2 = recessive homozygous frequency (aa)

Answer 76

- No migration - no natural selection - an infinite population size - random mating - no mutation

Answer 77

- No migration - no natural selection - an infinite population size - random mating - no mutation

Answer 78

- gene flow - non-random mating - mutation - genetic drift - natural selection