Medical Genetics Chapters 10 + 11

Monomer

a molecule that can be bonded to other identical molecules to form a polymer.

Thalassemias Disorders:

associated with an imbalance in the production of alpha or beta globin.

Monosaccharides are

glucose, fructose, galactose

Polysaccharides are

glycogen, starch, cellulose, (complex carbs)

Direct modifications

Chemicals can also alter bases in DNA and their base pairing properties. Some mutagens do this by directly changing one base into another. For example, treatment of DNA with nitrous acid (HNO2 ) changes cytosine into uracil.

What are mutation rates effected by?

Gene Size, presence of specific nucleotide repeats,

Supertasters for the chemical PTC are ____ for the trait.

Homozygous dominant

Explain how lactose is broken down?

Lactose - Glucose Galactose Galactose - 1 - phosphate UDP - Galactose

Describe the breakdown of lactose?

Lactose - Glucose or Galactose: Galactose-1-phosphate - UDP-Galactose.

Gene Switching

When medications are used to 'switch on' non-mutant genes.

Do cells have repair mechanisms? How many genes are devoted to repair?

Yes of course:) The human genome contains more than 175 genes devoted to DNA repair.

Product

the specific compound that results from the enzymatic reaction. *Also the substrate for the next reaction.

Methylation

adding methyl groups to DNA in promoters, DNA methylation occurs almost exclusively on cytosine bases adjacent to a guanine base. Increased methylation reduces transcription

Galactosemia

autosomal recessive, Accumulation of toxic levels of galactose-1-phosphate, Symptoms of intellectual disability and blindness range from mild to severe. (Treated by a low galactose diet)

Several lines of research provide strong evidence that ____ to environmental signals influence behavior.

epigenetic responses

Epigenetic trait:

phenotype that is produced by epigenetic changes to DNA.

Mutagens:

physical or chemical agents that cause mutations. *Radiation and chemicals.

Spontaneous mutations

random change in the DNA due to errors in replication that occur without known cause

Promoter:

regulatory region located at the beginning of a gene.

Induced mutations

result from exposure to known mutagens

Hba is composed of?

two alpha globins and two beta globins. Members of the alpha globin gene family are clustered on chromosome 16 and the beta globin gene family is located on chromosome 11.

What is the first stage of DNA repair?

DNA polymerase proof reading.

Several genetic disorders, including Fanconi anemia and ataxia telangiectasia, are caused by mutations in ____.

DNA repair genes

PBDEs

(short for polybrominated diphenyl ethers), are chemically related to well-known and persistent environmental contaminants such as PCBs that cause cancer and other health problems in humans. In humans, PBDEs have been linked to disruptions in thyroid hormone production, developmental defects in children, genital abnormalities in males, and, as mentioned, possibly cancer.

Sickle Cell Anemia

*Autosomal recessive disease The mutation in sickle cell anemia affects the beta globin component of hemoglobin. After oxygen is transferred to cells in the body, hemoglobin molecules with mutant beta globin subunits stick together and form long fibers in the cytoplasm. These fibers distort and harden the membrane of the red blood cell, twisting the cell into a characteristic sickle shape. *The disease is caused by a change in only one of the 146 amino acids in beta globin.

Whole-genome sequencing - indirect observation.

1 in 100,000,000 (1 x 10-8)

Cells that accumulate a lot of DNA damage can have several fates:

1. The cells can become dormant, a condition called senescence. 2. Control systems in the cell can induce cell suicide, a process called apoptosis. 3. The accumulated mutations cause the cell to escape the normal controls of the cell cycle and become cancerous.

How many bases are in the human genome?

6 billion

Ecogenetics

A branch of genetics that studies genetic traits related to the response to environmental substances.

Base Analog

A chemical compound that is sufficiently similar to normal nitrogen bases of DNA that it can be incorporated into DNA in place of a normal base. They have pairing properties unlike normal bases and can cause mutations during DNA replication. A source of induced mutation.

metabolic pathways are

A series of linked cellular reactions, facilitated by enzymes.

Phenylalanine

An essential amino acid found in milk, eggs, and other foods

How many new genetic mutations are present in newborn?

Approx. 60

Direct observation/measurement of particular genes mutation rate?

Average = 1 in 100,000 (1 x 10-5)

How does the tightness of DNA around histones effect transcription?

DNA can be wound to various degrees of 'tightness' to inhibit or encourage transcription. The control region of a gene is called the promoter. If the promoter is tightly wound around histones, the gene cannot be expressed because the promoter is not available for transcription by RNA polymerase. However, if the histone molecules associated with the promoter are chemically modified, their association with DNA is loosened, making the promoters available for transcription

How many hemoglobin molecules are in each RBC?

Each RBC contains around 280 million molecules of hemoglobin. Around 5.6 × 10^14 new hemoglobin molecules are produced per second.

What happens when a mutation stops the activity of a particular enzyme?

Explain. Key points: 1 - All subsequent reactions stop. 2 - Accumulation of substrate molecules at defective step.

Are autosomal recessive mutations detectable?

Not really! If an autosomal recessive trait suddenly appears in a family, only homozygous individuals are affected, and it is usually difficult or impossible to trace the mutant allele through previous generations to identify the person or even the generation in which the mutation first occurred.

What type of mutations can be inherited?

Only mutations in germ cells can be passed onto future generations.

Explain how the parathion pesticide is a good example of ecogenetics?

Parathion is converted to the toxic metabolite paraoxon. Paraoxon is inactivated by enzyme paraoxonase. Different paraoxonase alleles determine the rate of paraoxon metabolism, and therefore resistance or susceptibility to its toxic effects.

Translation

Process by which mRNA is decoded and a protein is produced

Why is radiation harmful to cells?

Radiation can cause biological damage at several levels. As radiation strikes the molecules in cells, it creates charged atoms called ions. Such ionized molecules are highly reactive and can cause mutations in DNA. Because cells are about 80% water, radiation often splits water into hydrogen ions (H+ ) and hydroxyl radicals (.OH). Free radicals can produce mutations if they interact with DNA.

What is radiation?

Radiation is the transfer of energy by electromagnetic waves.

types of background radiation

Radon, Cosmic, Terrestrial, Internal, Medical x-rays, Nuclear medicine, consumer products

What is the second stage repair mechanism of DNA?

Repair enzymes. Cut out the mismatched/bulging DNA + its neighbors and let DNA polymerase try again. *Repair enzymes don't always cut out the correct base.

PKU (phenylketonuria)

Results in the buildup of phenylalanine and phenylpyruvic acid, damaging the developing newborn brain.

Trinucleotide repeats.

Sets of three nucleotide bases that are repeated. *Predisposes for mutation.

Why do some genes have different mutation rates?

Some of the factors known to influence the mutation rates of some genes include: gene size and the presence of certain nucleotide repeats.

Hemoglobin

The adult form of hemoglobin, called HbA, is a composite of four protein molecules called globins. *Each globin molecule carries an iron-containing heme group. (Where oxygen binds)

Pharmacogenomics

The development of customized drugs for disease treatment tailored to an individual's genetic makeup.

Tautomeric shift

The purine and pyrimidine bases in nucleotides can exist in alternate chemical forms that depend on small atomic changes within the molecule called tautomeric shifts. When a tautomeric shift occurs in Adenine it can bond to Cytosine. When a tautomeric shift occurs in Thymine it can bond to Guanine.

Pharmacogenetics

The study of genetic variations that underlie the differences in individuals' responses to drugs

Do our epigenetics make us who we are?

Yes, well kinda:) Several lines of research provide strong evidence to the idea that epigenetic responses to environmental signals during prenatal development or in early life influence behavior (and physical health) during adulthood.

Polymer

a large molecule, or macromolecule, composed of many repeated subunits.

Millirem:

a rem is a measure of radiation dose equal to 1,000 millirems.

Mutations are changes in the nucleotide sequence of DNA that ____.

can be passed on to daughter cells. (So somatic mutations aren't mutations?)

Impact of proteins

cell structure, metabolic reactions, hormonal responses, cell-to-cell signaling systems, gene expression, the immune system, and much more:)

Nonsense mutations:

change codons for amino acids into one of the three stop codons: UAA, UAG, or UGA.

Hemoglobin variants:

genetic disorder were amino acid sequence changes within globins. *Alpha and beta globins with variant amino acid sequences. *More than 90% of all hemoglobin variants have a single amino acid substitution in the globin chain and 60% of these are found in beta globin.

Allelic expansion

increase in gene size caused by an increase in the number of trinucleotide repeat sequences

Galactosemia (MIM 230400):

is an autosomal recessively inherited disorder caused by the inability to break down galactose, one of the two sugars found in lactose. Galactose metabolism is disrupted, and a compound called galactose-1-phosphate accumulates and reaches toxic levels in the body. *There are three different alleles affecting Galactosemia: g, G and G^D. G^D has 50% of normal enzymatic activity.

Lactose intolerance

is not considered a genetic disorder but only a variation in gene expression. In some populations, lactase activity persists in adults as a dominant trait, giving them the ability to digest lactose. In populations around the world, the frequency of lactose intolerance varies from 0% to 100%. *In most human populations, lactase levels are highest soon after birth and drop off in middle-to-late childhood. As a result, older children and adults have less than 10% of the lactase activity found in infants.

Nucleosome:

is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer.

Mutations in genes that encode enzymes are not limited to amino acid metabolic pathways. Other affected pathways include:

lipid metabolism, nucleic acid metabolism, and carbohydrate metabolism.

Mutation rates of human genes are expressed as the number of ____.

mutated alleles per gene in each generation

Frameshift mutations:

mutational events in which a number of bases (other than multiples of three) are added to or removed from DNA, causing a shift in the codon reading frame. *These mutations cause large-scale changes in the amino acid sequence and alter the structure and function of the derived protein.

Missense mutations:

mutations that cause the substitution of one amino acid for another in a protein.

Sense mutations

mutations that change a termination codon into one that codes for an amino acid. Such mutations produce elongated proteins.

Nucleotide substitutions:

mutations that involve replacement of one or more nucleotides in a DNA molecule with other nucleotides. *Alter the sequence but not the number of nucleotides. *Typically involve a small number of nucleotides.

Genetic imprinting

selective expression of either the maternal or paternal copy of a gene. *Caused by epigenetic changes to DNA. *Methylation of promoter regions imprints and silences either the maternal or paternal copy of a gene. *Imprinting does not affect all genes. Only genes in certain regions of seven human chromosomes are known to be imprinted. Some of these are regions on the short arm of chromosome 4, the long arm of chromosome 15, and both arms of chromosome 18.

Disaccharides are

sucrose, lactose, maltose

metabolism

sum of all the biochemical reactions in an organism

Transcription (RNA Polymerase)

synthesis of an RNA molecule from a DNA template

Epigenome:

the epigenetic state of a cell.

Mutation rates

the number of mutated alleles (or "mutation events") per locus, per generation

In sickle cell anemia, affected individuals carry ____.

the same single nucleotide substitution

Substrate

the specific compound acted on by an enzyme

Epigenetics:

the study of heritable chemical modifications of chromosomal DNA (such as methylation of bases) and/or associated histone proteins that change the pattern of gene expression without affecting the nucleotide sequence of the DNA.

Rem:

the unit of radiation exposure used to measure radiation damage in humans. It is the amount of ionizing radiation that has the same effect as a standard amount of X-rays.