Assignment: Extensions to Mendelian Genetic & Extrachromosomal Inheritance Questionnaire

Assignment: Extensions to Mendelian Genetic & Extrachromosomal Inheritance Questionnaire

Genetics: epigenetics 10-29-21 Chapter 19 Gene expression regulation • Transcriptionally (turning a gene on or off → making mRNA) • Post-transcriptionally • mRNA modification, RNAi, etc • Translation (mRNA → protein), post-translational modifications • Not enough to explain how all phenotypes arise • Identical twins that aren’t completely identical • X-inactivation • Maternal vs paternal expression • Genome modifications that don’t change sequence: epigenetics! Epigenetics Epigenetics • An epigenetic trait is a stable, mitotically and meiotically heritable phenotype that results from changes in gene expression without alterations in the DNA sequence • Epigenetics is the study of the ways in which these changes alter celland tissue-specific patterns of gene expression • The epigenome refers to the epigenetic state of a cell • Epigenome differs between cells-types! • During its life span, an organism has one genome, but this genome can be modified in diverse cell types at different times to produce many epigenomes Epigenetics • Classical regulatory mechanisms cannot fully explain how some phenotypes arise • Interaction between an individual’s genome and epigenome • Epigenetic changes lead to phenotypic changes throughout the organism’s life cycle Epigenetics has been implicated in • Progressive restriction of gene expression during development .

Assignment: Extensions to Mendelian Genetic & Extrachromosomal Inheritance Questionnaire

• Allele-specific expression in gene imprinting • Environment genome interactions during prenatal development that affect adult phenotypes • Changes in gene expression throughout lifespan • Abnormal regulation of the epigenome leads to human genetic disorders such as: • Prader–Willi syndrome • Angelman syndrome • Beckwith–Weidemann syndrome • The loss or alteration of other epigenetic states can result in cancer Epigenetic Alterations to the Genome • Epigenetic changes occur through three major mechanisms: • Methylation of DNA • Reversable; addition or removal of methyl groups • Histone modification and chromatin remodeling • Alter the accessibility of genes for transcription • Noncoding RNA Methylation of DNA • One of the three major epigenetic mechanisms is the reversible modification of DNA by the addition or removal of methyl groups • In mammals, methylation of the DNA takes place after replication and during differentiation of adult cells • Methylation involves the addition of a methyl group catalyzed by methyltransferase enzymes • Addition of a methyl group (-CH3) to cytosine on the 5-carbon of the cytosine nitrogenous base resulting in 5methylcytosine (5mC) • Reaction catalyzed by a family of enzymes called DNA methyltransferases (DNMTs) Methylation of DNA → gene silencing • Methylation occurs on cytosine bases adjacent to guanine called CpG dinucleotides, which are clustered in regions called CpG islands • CpG islands are located in and near promoter sequences adjacent to genes • CpG Islands adjacent to essential genes (housekeeping genes) and cell-specific genes are unmethylated and available for transcription • Other genes are methylated and transcriptionally silenced Methylation.

Assignment: Extensions to Mendelian Genetic & Extrachromosomal Inheritance Questionnaire

• The added methyl groups occupy the major groove of D N A and silence genes by blocking the binding of transcription factors and other proteins necessary to form transcription complexes • Cell-type specific gene silencing • Tissue types have different methylation patterns • Bladder vs bone/cartilage vs heart/blood vessels vs bone marrow Methylation patterns in tissues & species • Can lead to disease susceptibility & progression • Non-alcoholic fatty liver disease • Not all species use 5mC • Algae, worms, flies rely on 6mA • Pretty new finding • Think it’s how epigenetic information is transmitted to offspring Methylation: not just for genes • The bulk of methylated CpG dinucleotides are found in repetitive DNA sequences located in heterochromatic regions of the genome including the centromere • Heterochromatic methylation: • Maintains chromosome stability by preventing translocations and other chromosomal abnormalities • X chromosomes in mammalian females are inactivated by converting them into heterochromatin (dosage compensation) • CpG methylation in euchromatic regions causes a parent-specific pattern of gene transcription Histone Modification • Histone modification is an important epigenetic mechanism of gene regulation • Chromatin is composed of DNA wound around an octamer of histone proteins to form nucleosomes • Amino acids in the N-terminal region of the histones can be covalently modified by acetylation, methylation, and phosphorylation Histone Modification • Modifications occurs at conserved amino acid sequences in the N-terminal histone tails, which protrude from the nucleosome.

• Chemical modification of histones alters the structure of chromatin, making genes accessible or inaccessible for transcription Histone Modification • Acetylation by histone acetyltransferase (HAT) opens up the chromatin structure • Makes genes available for transcription • Removal of the acetyl groups by histone deacetylase (HDAC) closes the configuration • Silences genes by making them unavailable • Methylation of histones • Can activate or repress expression • Phosphorylation represses Histone Modification • The histone code • The sum of the complex patterns and interactions of histone modifications that change chromatin organization and gene expression Non-coding RNAs: miRNA • Small, noncoding RNA molecules also participate in epigenetic regulation of gene expression • After transcription, these miRNA (microRNA) molecules associate with protein complexes to form RNA-induced silencing complexes (RISCs) lncRNA • Long noncoding RNA (lncRNA) share many properties with mRN As • 5′ caps • 3′ poly-A tails • Splicing of introns • NO CODING SEQUENCE! • Four classes of lncRNA loci (associated with nearby genes) 1. Antisense 2. Intronic 3. Bidirectional 4. Intergenic lncRNA • Unlike mRNA, lncRNAs lack frame that codes for the insertion of amino acids into a polypeptide • lncRNA binds to chromatin-modifying enzymes • Affects chromatin modification and gene expression Epigenetics and Monoallelic Gene Expression • Monoallelic expression (MAE) • Only one allele is transcribed, while the other allele is transcriptionally silent • There are three major classes of MAE 1. Parent-of-Origin Monoallelic Expression: Imprinting 2. Random Monoallelic Expression: Inactivation of the X Chromosome 3. Random Monoallelic Expression of Autosomal Genes Epigenetics and Imprinting • Imprinted genes show expression of only the maternal allele or the paternal allele • This parent-specific pattern of allele expression occurs during gamete formation • Differential methylation of CpG-rich regions produces allele-specific imprinting and subsequent gene silencing Epigenetics and Imprinting.

• Once a gene has been methylated and imprinted, it remains transcriptionally silent during embryogenesis and development • Most imprinted genes direct aspects of growth during prenatal development • In mice, genes on the X chromosome are expressed in the placenta, but genes on the paternal X chromosome are silenced Epigenetics and Imprinting • The pattern of imprinting in mammals is reprogrammed every generation • When gamete formation begins in female/male germ cells, both chromosome sets have their imprints erased and are each reprogrammed by changing the pattern of methylation to carry a female/male imprint that is transmitted to the next generation through the egg/sperm • Reprogramming occurs in the parental germ line and in the developing embryo just before implantation • After implantation, differential genomic remethylation recalibrates which maternal and paternal alleles will be inactivated Epigenetics and Imprinting • Most imprinted genes encode growth factors or other growth-regulating genes • Most imprinting disorders have their origins during fetal growth and development • Prader–Willi syndrome, Angelman syndrome, and Beckwith– Weidemann syndrome • BWS is a disorder of imprinting • Caused by abnormal patterns of DNA methylation resulting in altered patterns of gene expression Genetics: Mapping pt 2 & extrachromosomal inheritance 10-27-21 Three-Point Mapping • Three criteria of three-point mapping • Parent must be heterozygous for all three genes under consideration • Phenotypic class must reflect genotype of gametes of parents • Sufficient number of offspring must be produced for representative sample Three-Point Mapping • Noncrossover F2 phenotypes • Occur in greatest proportion of offspring.

• Double-crossover (DCO) phenotypes • Occur in the smallest proportion • Reciprocal classes of phenotypes • F2 phenotypes complement each other • Derived from heterozygote • Have wild type and mutant for all three genes Determining gene sequence • Determining gene sequence: • Method 1 based on three possible arrangements of genes • Start with determining F1 female alleles • Assume all orders possible • Compare to actual cross progeny phenotypes • If you predict y is in the middle, you expect to see DCO with y being the odd gene out • If y is not, then your prediction is wrong. W or ec is in the middle Determining gene sequence • Determining gene sequence: • Method 1 based on three possible arrangements of genes • Method 2 uses three possible arrangements • Also considers doublecrossover event As the Distance between Two Genes Increases, Mapping Estimates Become More Inaccurate • Expected frequency of multiple exchanges between two genes predicted from distance between them • Genes farther apart increase the probability of undetected crossovers Interference (I) • Interference • Inhibition of further crossover events • Inhibited by another crossover event nearby • Reduces expected number of multiple crossovers • Calculated to quantify disparities that result from interference • Coefficient of coincidence (C) Observed DCO C= Expected DCO • Interference: I = 1 − C Positive and Negative Interference • Interference • Complete when no double crossovers occur • Positive: Fewer double-crossover events than expected occur • I is a positive number • Negative: More double-crossover events than expected occur • I is a negative number Positive and Negative Interference • Two genes close together • Positive interference occurs • Accuracy of mapping is high • Distance between genes increases • Interference decreases • Accuracy of mapping decreases Drosophila gene mapping • Large number of mutants in organisms such as • Drosophila • Maize • Mice • Allows for construction of extensive chromosome mapping Chromosome Mapping is Now Possible Using DNA Markers and Annotated Computer Databases • DNA markers • Short segments of DNA with known sequence and location • Useful landmarks for mapping • Earliest examples of DNA markers: • RFLPs and microsatellites • SNPs: Single-nucleotide polymorphisms • Found throughout genome • Used by geneticists to identify and locate related genes • Used to screen for diseases • Example: Cystic fibrosis Physical vs genetic maps • Physical = distances between genes in base pairs • Genetic maps = based on relative distances (recombination rates) between genes (map units, cM) • Can be wide variation between physical & genetic maps

Assignment: Extensions to Mendelian Genetic & Extrachromosomal Inheritance Questionnaire

Important information for writing discussion questions and participation

Welcome to class

Hello class and welcome to the class and I will be your instructor for this course. This is a -week course and requires a lot of time commitment, organization, and a high level of dedication. Please use the class syllabus to guide you through all the assignments required for the course. I have also attached the classroom policies to this announcement to know your expectations for this course. Please review this document carefully and ask me any questions if you do. You could email me at any time or send me a message via the “message” icon in halo if you need to contact me. I check my email regularly, so you should get a response within 24 hours. If you have not heard from me within 24 hours and need to contact me urgently, please send a follow up text to

I strongly encourage that you do not wait until the very last minute to complete your assignments. Your assignments in weeks 4 and 5 require early planning as you would need to present a teaching plan and interview a community health provider. I advise you look at the requirements for these assignments at the beginning of the course and plan accordingly. I have posted the YouTube link that explains all the class assignments in detail. It is required that you watch this 32-minute video as the assignments from week 3 through 5 require that you follow the instructions to the letter to succeed. Failure to complete these assignments according to instructions might lead to a zero. After watching the video, please schedule a one-on-one with me to discuss your topic for your project by the second week of class. Use this link to schedule a 15-minute session. Please, call me at the time of your appointment on my number. Please note that I will NOT call you.

Please, be advised I do NOT accept any assignments by email. If you are having technical issues with uploading an assignment, contact the technical department and inform me of the issue. If you have any issues that would prevent you from getting your assignments to me by the deadline, please inform me to request a possible extension. Note that working fulltime or overtime is no excuse for late assignments. There is a 5%-point deduction for every day your assignment is late. This only applies to approved extensions. Late assignments will not be accepted.

If you think you would be needing accommodations due to any reasons, please contact the appropriate department to request accommodations.

Plagiarism is highly prohibited. Please ensure you are citing your sources correctly using APA 7th edition. All assignments including discussion posts should be formatted in APA with the appropriate spacing, font, margin, and indents. Any papers not well formatted would be returned back to you, hence, I advise you review APA formatting style. I have attached a sample paper in APA format and will also post sample discussion responses in subsequent announcements.

Your initial discussion post should be a minimum of 200 words and response posts should be a minimum of 150 words. Be advised that I grade based on quality and not necessarily the number of words you post. A minimum of TWO references should be used for your initial post. For your response post, you do not need references as personal experiences would count as response posts. If you however cite anything from the literature for your response post, it is required that you cite your reference. You should include a minimum of THREE references for papers in this course. Please note that references should be no more than 5 years old except recommended as a resource for the class. Furthermore, for each discussion board question, you need ONE initial substantive response and TWO substantive responses to either your classmates or your instructor for a total of THREE responses. There are TWO discussion questions each week, hence, you need a total minimum of SIX discussion posts for each week. I usually post a discussion question each week. You could also respond to these as it would count towards your required SIX discussion posts for the week.

I understand this is a lot of information to cover in 5 weeks, however, the Bible says in Philippians 4:13 that we can do all things through Christ that strengthens us. Even in times like this, we are encouraged by God’s word that we have that ability in us to succeed with His strength. I pray that each and every one of you receives strength for this course and life generally as we navigate through this pandemic that is shaking our world today. Relax and enjoy the course!

Hi Class,

Please read through the following information on writing a Discussion question response and participation posts.

Contact me if you have any questions.

Important information on Writing a Discussion Question

• Your response needs to be a minimum of 150 words (not including your list of references)
• There needs to be at least TWO references with ONE being a peer reviewed professional journal article.
• Include in-text citations in your response
• Do not include quotes—instead summarize and paraphrase the information
• Follow APA-7th edition
• Points will be deducted if the above is not followed

Participation –replies to your classmates or instructor

• A minimum of 6 responses per week, on at least 3 days of the week.
• Each response needs at least ONE reference with citations—best if it is a peer reviewed journal article
• Each response needs to be at least 75 words in length (does not include your list of references)
• Responses need to be substantive by bringing information to the discussion or further enhance the discussion. Responses of “I agree” or “great post” does not count for the word count.
• Follow APA 7th edition
• Points will be deducted if the above is not followed

• Remember to use and follow APA-7th edition for all weekly assignments, discussion questions, and participation points.
• Here are some helpful links
• The is a great resource