Genetics Test 3 - Test cheat sheet PDF

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X-Linked Dominant & X-Linked Recessive Mutations, & the Y chromosome. Chapter 6 PP#1 CHOOSE A DISEASE AND BECOME EXPERT a. X-linked recessive- Hemophilia b. X-linked dominant- Incontinentia pigmenti 1. Look at the pedigrees. How many copies of the affected allele are required to produce the trait? Could there be exceptions to this? a. In males they only need one mutant copy but females need two copies of the gene to be affected. However females can be carriers and have only half the usual amount of coagulation factor VIII or coagulation factor IX, which generally enough for regular blood clotting. b. In females only one is needed to cause the disease,if they are homozygous it is lethal, it is lethal in males so few males are born with it, some males may be born with mild effects of the mutation in only some cells or an extra copy of the x chromosome in each cell 2. Provide a pedigree with a reasonable number of affected individuals. Label every genotype, to show that you understand the mode of inheritance. a. Look in notebook 3. Does the mutation result in a gain-of-function or loss-of-function? Why? Meaning? a. Loss-of-function, loss of coagulation factor VII or IX 4. What causes the disease? How common is it? Why? a. Genetic mutation, males A 1in4,000 to 1in5000, male B 1in20000 because it is a recessive mutation b. Only occurs in females as it is fatal in males, 5. How many known mutations contribute to the disease? a. One mutation on the F8 or F9 gene lead to the abnormal production of the coagulation proteins b. Genetic mutation localized on the chromosome Xq28 6. Does it exhibit pleiotropy, lethality, or incomplete penetrance/variable expressivity? Explain. Are there multiple alleles that contribute to variable symptoms among individuals? a. b. Chapter 6 PP#2 Barr bodies- a small, densely staining structure in the cell nuclei of female mammals, consisting of a condensed inactive X chromosome. It is regarded as diagnostic of genetic femaleness. Xist gene- non-protein coding gene Xist RNA- acts as a major effector of the x inactivation process Methylation- addition of a methyl group to a DNA strand to control gene expression Silencing- regulation of gene expression X-inactivation and Atypical Chromosome Numbers

1. Why are trisomy 21 children mentally impaired due to the extra autosomal genes, but the following trisomies or monosomies are typically of normal intelligence? a. Poly X syndrome (47,XXX) Pretty much normal, just a little taller b. Klinefelter’s Syndrome (47,XXY) Some feminization, sterile, tall c. Jacob’s Syndrome (47,XYY) More testosterone, taller, not enough for aggression d. Turner’s Syndrome (XO) Webbed neck or broad shoulders, sterile 2. Other Klinefelter’s abnormalities (XXXY, XXXXY, XXXYY, XXYY) or Poly X Syndrome (XXXX), show some mental impairment, but not to the degrees of Trisomy 21. The following two hypotheses have been proposed. What are the implications of each? a. X-inactivation occurs ~16 days after fertilization (implications)? All being expressed in the first 16 days and it is unknown what causes it, having more X’s expressed in the beginning or having more genes expressed through improper methylation throughout life. Theory about Turner’s that the second X is required in the first 16 days b. A few genes on the pseudo-autosomal regions of the ‘X’ chromosomes escape inactivation (implications)? Genes remaining inexpressed 3. Between the ages of ~15-45, an oocyte is sitting in Prophase I in the ovaries. What are explanations for non-disjunction and the ‘maternal age effect’? What is the method, and replacement as tools to ‘cure’ Down’s Syndrome?

Exam 3 Review Topics - Spring 2017 Ch. 5: Beyond Mendel’s Laws: Review these concepts. Do practice problems in packet. I also asked you to find as many connections as you can for each term, to expeditions #1 cancer, and we did connections to SCD/SCT in class. 1. Lethal Alleles- alleles that cause the death of the organism that carry them 2. Multiple Alleles- any one series of three or more alternative or allelic forms of a gene 3. Incomplete Dominance- form of intermediate inheritance in which one allele for a specific trait is not completely expressed over its paired allele 4. Codominance- a form of dominance in which the alleles of a gene pair in a heterozygote are fully expressed thereby resulting in offspring with a phenotype that is neither dominant nor recessive 5. Penetrance & Expressivity- unlike penetrance, expressivity describes individual variability, not statistical variability among a population of genotypes

6. Pleiotropy- the production by a single gene of two or more apparently unrelated effects 7. Genetic Heterogeneity- is a phenomenon in which a single phenotype or genetic disorder may be caused by any one of a multiple number of alleles or nonallele(locus) mutations 8. Phenocopies- an individual showing features characteristic of a genotype other than its own, but produced environmentally rather than genetically Ch. 5 - Mitochondrial Inheritance: (These are also in the packet). Mitochondrial inheritance and pedigrees to track lineage through the female and heteroplasmy. Also answer the questions below, some may appear on the exam: a) How are mitochondrial traits transmitted to the offspring of both sexes and Why? Mitochondrial traits are transmitted to the offspring of both sexes through the mother as you do not possess your own mitochondrial DNA you have your moms mitochondrial DNA. b) Why does mitochondrial DNA mutate faster than nuclear DNA? Mitochondrial DNA is subject to more damage from reactive oxygen molecules released during reactions and lacks the DNA repair mechanisms found in the nucleus c) A variety of disorders that cause muscle weakness and fatigue result from mutations in mitochondrial genes. What are these disorders called, and why are they so rare? Mitochondrial disease and it is rare because there is a certain threshold that needs to be reached before it will be expressed. Once considered rare, heteroplasmy is now known to occur in one-tenth of mitochondrial bases. Why are the most serious diseases ‘heteroplasmic’ rather than homoplasmic? When you are heteroplasmic you have a good copy of the gene and a bad copy of the gene, not all cells are going to express it the same way too so you can have one cell with an over abundance of the bad gene and one that is predominantly the good gene leaving all cells different.

What is the difference between mitochondrial DNA and nuclear DNA, and why is mitochondrial DNA typically used for forensic analysis over nuclear DNA? (Provide 2 reasons).

Nuclear DNA is specific to the person while mitochondrial DNA is passed down from mother to child and it can be easier to track who it is from and it will better show who you are related to. What if you inherit mutated DNA with your normal DNA? Why, within a family, do we see variably expressivity? If your body catches it early enough it can be changed before it is expressed and can be multiplied. You can see it is expressed through the family if it is in the mitochondrial DNA and you can see a pattern if it is inherited in the nuclear DNA. Understand mitochondrial pedigrees (i.e the pedigree of the Romanov family in packet). Ch. 5 (D2L reading) Recombination & Linked genes in humans. Gene Mapping. Read this section of Ch. 5. You are not responsible for packet questions on linkage mapping - omit those questions. Be aware that Linkage maps are classical genetic maps based on crossover frequencies- (See the Nail Patella pedigree you evaluated). Physical maps are used today in which every nucleotide is sequenced). Show two independently assorting genes (unlinked) vs two linked genes (=a linkage group). Look in notebook Dihybrid test-crosses as the parents are used to detect linked genes and recombination. Look at the Nail Patella pedigree and locate the testcross used to detect recombination. Cis orientation of 2 genes in the test-cross heterozygote before crossing-over occurs, means both dominant genes are carried on the same homolog. Trans orientation has the two dominat genes on op Be comfortable with the two pedigrees I gave you on the handouts. (That’s all). Human Sex Determination – Ch. 6 – powerpoints, packet questions, and text: Homologous pairs? autosomes vs sex chromosomes Everybody has 22 homologous pairs autosomes and 1 pair of sex chromosomes either XX for females, or XY for males Pseudoautosomal regions vs. male specific region of Y (MSY): How do genes in the pseudoautosomal region of the Y chromosome differ from genes in the MSY? Importance of X and Y? Sex ratios at conception, birth, vs. later (why the difference)?

Use superscript symbolism for X-linked genes – i.e. XY, XcY, XX, XcX or XcXC Hemizygous vs Homozygous vs Heterozygous (Carriers) The Y chromosome; usefulness of Y-linked genes as “DNA Markers” to follow lineages – explain why. Euchromatin vs Heterochromatin – what does this refer to on the Y chromosome? Heterochromatin has a tighter DNA packaging than euchromatin. Euchromatin is usually under active transcription X-linked dominant & recessive vs. Y-linked pedigrees – be comfortable with symbols (review last exam), rules for each; be able to plug in correct genotypes and propose an inheritance pattern for the disease. SRY gene: Describe the phenotype of a person with an SRY gene deleted, mutated, or added. (How could this happen)? The phenotype would be a female with and XX phenotype with testicles despite not having a Y chromosome.The SRY gene is misplaced during the formation of the father's sperm cell. Describe the phenotype of an XY individual with a block in testosterone synthesis. Read up on one other divergence from the normal sexual development pathway (both autosomal recessive - in text – p. 114): Pseudohermaphrodite (5-alphareductase syndrome) Congenital Adrenal Hyperplasia (21 hydroxylase deficiency) Barr Bodies- a small, densely staining structure in the cell nuclei of female mammals, consisting of condensed inactive X chromosome Xist gene and RNA productX-inactivation- process by which one of the copies of the X chromosome present in female mammals is inactivated dosage compensation- mechanism by which the expression of X-linked traits is equalized in males, which have one X chromosome, and females, who have two. In mammals it is accomplished in the somatic cells of females

Look at the pedigrees (p. 99 packet). How many copies of the affected allele are required to produce the trait? Could there by exceptions to this? How? X-linked recessive you only need to have two copies of the allele, mainly male only diseases ex. Colorblindness and for a dominant x-linked pattern you only need to have one copy which is why it is found in both sexes

Provide a pedigree with a reasonable number of affected individuals. Label every genotype, to show that you understand the mode of inheritance. Does the mutation result in a gain-of-function or loss-of-function? Why? Meaning? What causes the disease? How common is it? Why? How many known mutations contribute to the disease? Does it exhibit pleiotropy, lethality, or incomplete penetrance/variable expressivity? Explain. Are there multiple alleles that contribute to variable symptoms among individuals? Genomic Imprinting: (You will not be responsible for the video clip described in the ppt. What is the hypothesized function of imprinting? Provide evidence from your text. Cite evidence from your text showing why the genetic contributions from both parents are necessary for normal prenatal development, i.e. development of the placenta vs. embryo development. Review the key concepts in the powerpoint – methylation, Prader-Willi vs. Angelman’s, IgF2 imprinting. Why does imprinting occur at all? 2 hypotheses. Show how Beckwith Wiedemann’s syndrome can be due to a uniparental disomy. Multifactoral Inheritance & GWAS (Text: Read Ch. 7 - p. 131 – Genes and environment mold traits and pp 139-142 – GWAS. Also read Ch. 20 p. 397 Matching patients to drugs). There are resources of commonly occurring single nucleotide polymorphisms (SNPs) in more than six hundred environmental response genes. These include a number of drug metabolism genes and many alleles of each gene. Pick a category from the handout (provided on Friday), and devise a genome-wide association study to identify SNPs associated with drug metabolism. Use your text and any other information as a guide. These questions will show up on Exam 3: Using genetic markers – SNPs – and lay out a “case-controlled design” for your GWAS. Explain what case-controlled means for your study. What biases are associated with this type of study in selecting ‘control’ individuals to participate, and even individuals with the disease? Are there any ‘true’ controls in a GWAS? Explain why or why not. If you locate some candidate associated with the SNPS through a GWAS, will these genes explain the cause of the disease? Why or why not?

List two general limitations to GWAS studies and one limitation unique to using GWAS for the drug metabolism study that you’ve chosen. Know the meaning of these with respect to GWAS: Genetic Markers (SNPs)- single nucleotide polymorphisms, each represent a difference in a single DNA building block. Case-controlled Studies- Looking at the phenotypes of people with the disease vs people without the disease, or for a particular phenotype, the in class dog fur example, Associations vs. Correlations- Association: shows if a genetic variant is associated with a disease or trait, a particular allele of a polymorphism will be seen more often than expected by chance in an individual carrying the trait. Correlation: estimate of the additive genetic effect that is shared between our pair of traits, self-reported mood and physiological reactivity could both be heritable, but their genetic correlation can tell you if they are likely to share the same genes Packet Question #4 (p. 104-106 in packet): 4. If you did a search regarding any ‘polygenic’ disease like obesity and added “Gene Network” to your search, you might come up with 100’s, maybe 1000’s, of genes that are expressed and have some association with obesity (see the simplified gene network below from p. 436 in your text): Use the multifactorial, polygenic disease Schizophrenia, to create a ‘Multifactorial Gene Network.” Read the two short articles on schizophrenia in the packet (pp. 104-107) and underline every concept or statement that discusses a genetic or environmental factor contributing to this disease. Genetic Networks are similar to concept maps, but serve a different purpose; scientists are trying to find relationships between genes and environmental factors and other diseases that were not previously associated. The network should highlight possible interactions between genes, environment, other diseases, and any factors that contribute to the abnormal expression of the disease. 1. Using genetic markers-SNPs- and lay out a “case-controlled design” for your GWAS. Explain what case controlled means for your study. 2. What biases are associated with this type of study in selecting ‘control’ individuals to participate, and even individuals with the disease? 3. Are there any ‘true’ controls in GWAS? Explain why or why not. 4. If you locate some candidate associated with the SNPs through GWAS, will these genes explain the cause of the disease? Why or why not? 5. List two general limitations to GWAS studies and one limitation unique to using GWAS for the drug metabolism study that you’ve chosen.

XXY XX XY XXX XXXY The highlighted X is inactivated, Barr Body, and you are stuck with whatever is on the activated X. The x to be inactivated creates it own mRNA that sets off methylation down the entire X to shut it down. Anything in excess of one X has a Barr Body, even on them there are at least a few genes that are still expressed from them due to improper methylation so they can still be read in certain locations....