GiM AfLs Flashcards
Shape of the mitochondrial genome?
Circular
The mitochondrial genome is a remnant of the ancestral chromosome of the symbiotic bacterium-like organism from which mitochondria are believed to have evolved. It replicates independently of the nuclear genome, and is also transmitted independently (cytoplasmic inheritance). When it comes to germline transmission, all of an embryo’s mitochondria derive from the oocyte (not the sperm), so that fathers cannot transmit mutations that lie within the small mitochondrial DNA circle. This is “non-nuclear” inheritance.
Okazaki fragments take part in which process to do with DNA?
Replication
Because the two strands of the DNA double helix run in opposite directions, only one of them can be copied continuously as the helix unwinds at the replication fork. The other must the made in chunks, each one initiated by an RNA primer. These Okazaki fragments must later be stitched (“ligated”) together.
A term used to describe how a genetic change manifests itself.
Phenotype
The O.E.D. definition of phenotype: “The sum total of the observable characteristics of an individual, regarded as the consequence of the interaction of the individual’s genotype with the environment; a variety of an organism distinguished by observable characteristics rather than underlying genetic features.”
This element is the most widespread class of retrotransposon in the human genome.
Alu
A large proportion of the genome comprises interspersed repeat elements that have dispersed around the genome by retrotransposition. Most of these “jumping” DNA elements are no longer active, but a small proportion are, so that new integration events occur every so often.
Vertical (parent to child) inheritance of a disorder is typically seen for autosomal ——– conditions.
Dominant
Autosomal dominant disorders are caused by heterozygous mutations, transmitted to offspring with a 50% probability.
This region of the chromosome separates the short and long arms.
Centromere
The centromere is seen down the microscope as a narrow region of the chromosome, where the sister chromatids are held together. This region is also crucial for attachment of the chromosome to the mitotic spindle (at the kinetochore).
Blocks of repetitive DNA sequence are found at the centromere and are required for its assembly, notably alphoid repeat sequences, which are unique to each chromosome and can be used as specific detection reagents.
Familial adenomatous _________ is an inherited condition that predisposes to bowel cancer.
Polyposis
Familial adenomatous polyposis (FAP) is also known as adenomatous polyposis coli (APC). It is an autosomal dominant condition in which thousands of benign polyps (adenomas) develop in the colon in early adult life. One or more of these eventually becomes a malignant colon cancer.
Parental consanguinity increases the risk of genetic diseases showing this inheritance pattern.
Recessive
Parental consanguinity increases the risk that a couple will both be carriers of the same recessive mutation. Rare recessive diseases therefore occur with increased frequency in such families.
This type of enzyme synthesizes DNA and RNA.
Polymerase
Polymerases are diverse in their biochemical properties, including whether they make DNA or RNA. They are, of course, vital biological molecules, but have also been co-opted by scientists for use as laboratory tools.
This term is used to refer to increasing severity of an inherited disease as it passes down successive generations.
Anticipation
Anticipation can be an “ascertainment artefact” (milder disease only noticed in a parent after referral of a more severely affected child) but has a real biological basis for some disorders.
A unit of chromatin, comprising about 200 bp of DNA wound around a histone core.
Nucleosome
Nucleosomes are the first level of assembly of the genome into chromatin. The histones are not just passive building blocks – they play an important role in gene regulation, through a large range of chemical modifications.
Ours consists of 46 chromosomes and was first correctly defined in 1956.
Karyotype
a. The chromosomal constitution of a cell (and hence of an individual, species, etc.) as determined by the number, size, shape, etc., of the chromosomes (usually, as observed at metaphase during cell division).
b. A systematized representation of the chromosomes of a cell or cells, esp. a photographic one.
Both these definitions of karyotype are from the O.E.D. and both are commonly used in genetics. The human karyotype was believed to have 48 chromosomes until correctly visualized for the first time.
An individual who is heterozygous for a recessive mutation.
Carrier
This is a somewhat imprecise term, but one that is quite widely used. The “carrier frequency” for some of the less rare recessive diseases may be quite high, raising the question of whether screening of individuals from the general population is justified or desirable.
That part of a gene which is excised from the RNA transcript by splicing.
Intron
Exons, which include the protein-coding part of the genome, are defined as the parts of the gene that end up in the mature spliced RNA product. They comprise about 2% of our DNA. Because most disease-causing mutations occur in exons, a popular “short-cut” version of genome analysis consists of sequencing all the exons—a so-called exome analysis. Introns separate the exons and must be precisely excised to allow “reconstruction” of the protein-coding mRNA.
The Philadelphia chromosome is characteristic of chronic ___________ leukaemia.
Myelogenous
The Philadelphia chromosome is a translocation between chromosomes 9 and 22: t(9;22)(q34;q11). It is found in the leukaemic cells of chronic myelogenous leukaemia (CML) and results in the production of an abnormal fusion protein BCR-ABL, due to the joining of the ABL and BCR genes on those two chromosomes. The BCR-ABL protein can be targeted with specific tyrosine kinase inhibitors that are effective in the treatment of CML.
An evolutionary remnant, in the form of a DNA sequence that resembles a gene elsewhere in the genome, but has mutations that appear to render it inactive.
Pseudogene
Pseudogenes have arisen during evolution by gene duplication, but have subsequently mutated and lost their functions. They are a normal widespread feature of the human genome. Because some of them are extremely similar in sequence to their functional siblings, they can interfere with laboratory analysis aimed at examining the functional gene.
A genetic change.
Mutation
Any genetic change is, by definition, a mutation. However, sometimes, the word is used in a way that implies that the change in question also has a phenotypic effect (particularly a harmful one).
An individual version or genetic variant at a particular locus.
Allele
The O.E.D. definition is nice and clear: “Each of two or more alternative forms of a gene that arise by mutation and which may be found in the same position on a homologous chromosome.” This is a “new word” invented by geneticists, but if you understand what is meant by it, and use it correctly, you will be much better placed to grasp any discussion dealing with genetic variation—which itself is central to why genetics affects human health.
What term describes a 45,XX,-21 chromosome makeup?
Monosomy
Autosomal monosomies are not compatible with life, but may be detected in spontaneous abortions. Monosomies may also develop as acquired abnormalities in tumour cells.
Advanced ** age is a major risk factor for numerical chromosome abnormalities
Maternal
The MYCN oncogene is characteristically amplified in this childhood tumour
Neuroblastoma
An example of somatic chromosome abnormality in cancer. Another common example is amplification of the growth factor receptor ERBB2 in breast cancer. These acquired genetic changes are important indicators of prognosis.
Cytogenetic technique that uses a DNA probe to examine a single locus
Fluorescent in situ hybridization (FISH)
Chromosomal inversion with both breakpoints on the same arm
Paracentric
pericentric = around the centromere (cf. pericardial = around the heart)
paracentric = beside the centromere (cf. parathyroid = beside the thyroid)
A type of translocation in which two acrocentric chromosomes are fused
Robertsonian
The vestigial short arms of acrocentric chromosomes differ in content from other chromosome arms. They contain no indispensible single-copy genes. What then is on the short arms of acrocentric chromosomes? (Look it up.)
Stage of cell cycle during which DNA replication occurs
Interphase
Interphase occupies most of the cell cycle duration. It is divided into G1, S and G2 phases, separated by regulatory checkpoints. DNA replication occurs during S (synthesis) phase, after which the cell has twice the normal DNA content. Consequently, when the chromosomes have later condensed and aligned on the spindle at metaphase, each chromosome is made up of two sister chromatids.
Turner syndrome (45,X) and Klinefelter syndrome (47,XXY) are examples of sex chromosome **
Aneuploidy
Situation in which there are two or more cell populations in an individual, differing in genetic makeup
Mosaicism
Mosaicism results from genetic changes that occur after the embryo has started to develop. In other words, these changes are due to mitotic errors, rather than meiosis. An individual may be mosaic for a chromosome abnormality (e.g. mosaic trisomy 21) or for any other genetic change (like a point mutation). The consequences of mosaicism are difficult to predict, since they depend not only on the nature of the genetic change, but also on the spatial distribution of the mutant cells within the whole organism.
_____ CGH is the front-line method for testing for chromosomal imbalance
Array
You should understand that aCGH and similar methods cannot detect balanced rearrangements (e.g. balanced reciprocal translocations). Only dosage changes will be detected.
Set of chromosomes in an individual
Karyotype
Sanger sequencing depends on the synthesis of DNA strands in the presence of chain _______
Terminators
Chain-terminating nucleotide analogues (typically 2′,3′-dideoxynucleoside triphosphates, ddNTPs) produce sets of nested fragments, all ending with the same base (A,C,G or T). The sizes of these fragments then provide a read-out of the positions of that base in the sequence.
A _______ gene syndrome refers to a disorder in which genes that are adjacent are simultaneously affected by a chromosomal rearrangement
Contiguous
A good example is WAGR syndrome, caused by deletion of the adjacent WT1 and PAX6 genes.
Potentially life-threatening type of congenital malformation common in children with Down syndrome
Cardiac
About half of Down syndrome babies have a structural abnormality of the heart which may need urgent surgical repair. Gastrointestinal problems are also common, including duodenal atresia.
DiGeorge Syndrome is a common deletion syndrome on which chromosome?
Chromosome 22
Chemical group added to cytosine bases in genomic DNA after replication
Methyl
Very important for gene regulation
The set of all the exons in the genome
Exome
The exome is not a naturally occurring entity; it is a conceptual collection of all the discontinuous exon segments in the genome. There are ways to isolate all these segments for DNA sequencing, which is a 50-fold smaller job than sequencing the entire genome.
A genetic ** results in reduced diversity
Bottleneck
A type of translocation in which two different chromosomes exchange parts of chromosome arms.
Reciprocal
Said to be balanced if no material is lost or gained.
A splice _____ site is found at the 5’ end of each intron in a gene.
Donor
Splice donor and splice acceptor sites in the primary RNA transcript are recognized by the splicing machinery (“spliceosome”). They contain conserved sequence motifs, and mutations adjacent to the splice junctions are likely to impair splicing, and so are common causes of inherited disease.
These chromosomes have vestigial short arms.
Acrocentric
The short arms of acrocentric chromosomes differ in content from other chromosome arms. They contain no indispensable single-copy genes. What then is on the short arms of acrocentric chromosomes? (Look it up.)
Stretches of this amino acid are encoded by the trinucleotide repeats involved in some neurodegenerative disorders.
Glutamine
Glutamine (Gln, Q) is encoded by the codon CAG, and triplet repeats based on the sequence (CAG)n occur in a number of proteins. These repeats are generally polymorphic, but abnormally large repeat expansions result in the generation of proteins with larger than normal poly(Gln) stretches. The abnormal properties of these proteins result in neuronal damage, manifested through a variety of different late-onset neurodegenerative disorders. Anticipation is a feature of the inheritance of some of these.
This type of mutation is not heritable.
Somatic
Somatic mutations occur outside the germline. In general, that means that the cell in which a somatic mutation occurs will later give rise to daughter cells that differ from their surrounding colleagues. Provided such a mutation occurs early enough in development, the mutant cells may make up a substantial proportion of the individual. This is the situation known as mosaicism. Another consequence of somatic mutation (unusually later in life) is cancer, which is caused by a process of somatic mutation followed by selection of mutant cells and sequential further mutations.
Point of meiotic recombination.
Chiasm
Chiasmata are where crossing over between maternal and paternal chromosomes occurs during meiosis I. An essential part of gametogenesis, but also a source of errors resulting in chromosomal duplications and deletions.
The proportion of the multifactorial causation of a common disease that can be attributed to genetic factors.
Heritability
A tumour _____ gene is one that tends to prevent the emergence of the transformed phenotype in somatic cells
Suppressor
Inactivating mutations of tumour suppressor genes underlie many inherited cancer syndromes. You need to understand the Knudsen “two-hit” mechanism for this.
This type of codon can be TGA, TAA or TAG.
Stop or Terminator
Women with BRCA1 mutations are at high risk of this type of cancer
Breast, ovarian, melanoma
In men, prostate cancer is also higher risk.
Describes the substitution of a chemically similar amino acid
Conservative
This often hereditary childhood cancer involves the eye
Retinoblastoma
Term to describe “identical” twins.
Monozygotic
More than one gene contributes to the susceptibility to such a disease.
Polygenic
Simple Mendelian inheritance patterns will not be observed for polygenic disorders.
This syndrome results from a microdeletion including the elastin (ELN) gene.
Williams
An example of a chromosomal imbalance syndrome due to a recurrent microdeletion of a small region of Chr. 7q11. Because of the presence of flanking genomic repeat elements, the same region is recurrently deleted or duplicated. There are distinctive medical consequences, including infantile hypercalcaemia, supravalvular aortic stenosis and peripheral pulmonary stenosis. The neurodevelopmental profile is also quite characteristic. Nicely illustrated in various ways by this video from the US Williams syndrome association.
