POPH90111 Genetic Epidemiology

POPH90111 Genetic Epidemiology

Question 1

As a genetic epidemiologist, you decide to conduct a genome-wide association study for a disease called Machotic disease. The study includes 2,000 people with Machotic disease (cases) and 2,000 people without Machotic disease (controls). The cases and controls are frequency matched for age, sex and ethnicity i.e., the cases, on average, are the same age, have the same proportion of each sex, and the same proportion of ethnicities as the controls. You obtain the following genotype results of 3 of the 500,000 SNPs tested.

SNP and genotypeNumber of CasesNumber of Controls
rs191GG 1100 1210


Gregor’s disease is a rare disease resulting in patches of green wrinkly skin. One of the suspected causes for Gregor’s disease is a bacteria found in the soil of garden beds, because previous studies have shown that vegetable growers are more likely to develop the disease. However, other theories have been proposed for this association including confounding with pesticides.

As a genetic epidemiologist, your aim is to determine whether soil bacteria is actually a likely cause of Gregor’s disease. You decide to use Mendelian Randomisation to address this aim. You begin by conducting a case-control study by recruiting 2,000 people with Gregor’s disease (cases) and 2,000 people without Gregor’s disease (controls) and ask them to complete a questionnaire on their lifetime exposure to garden soil and pesticides. You also collect a DNA sample from the cases and control via a cheek swab and you genotype the cases and controls for the C allele of the SNP rs2019, which has been previously shown to make the carrier susceptible to any bacterial infection. The evidence to support this comes from a large previous study, which showed 15% of those with a C allele of the SNP rs2019 had a bacterial infection in the past year compared with 1% of those without a C allele.

You obtain the following results:

1) 40% of the cases (who have Gregor’s disease) and 25% of the controls (who do not have Gregor’s disease) have at least one C allele of the SNP rs2019.

2) Of those with at least one C allele of the SNP rs2019, 10% reported using pesticides once a year or more compared with 11% of those without a C allele.

Oscurophobia is a psychiatric disorder that rarely occurs in humans. People with Oscurophobia experience panic attacks when suddenly exposed to anything dark. Even wearing black or dark coloured clothes or looking into the dark spaces, results in high levels of anxiety. The causes of Oscurophobia are not well known but a proportion of the disease is known to be caused by an inherited mutation in the gene OS13. To date, only one inherited mutation has been identified in this gene: a substitution of a C for a T at base 2019 that results in an early stop codon. Approximately 0.2% of the population carry the T allele in OS13 (i.e., approx. 1 in 500 people carry one mutated allele) and they have an increased risk of Oscurophobia. The two penetrance studies conducted to date have reported different estimates of penetrance.

STUDY 1. People with a family history of Oscurophobia (probands) were recruited from a genetics clinic and tested for the T variant in OS13. If the proband was found to carry the T variant, then all known relatives were invited to participate in the study and were tested for the T variant. A survival analysis of carriers of the T variant (including the probands) was conducted. Carriers of the T variant had a cumulative risk to age 70 years of Oscurophobia of 65% (95% confidence interval, 52% to 76%).

STUDY 2. Recently diagnosed cases of Oscurophobia (probands) were recruited irrespective of having a family history and tested for the T variant in OS13. If the the proband was found to carry the T variant, their first- and second-degree relatives were then invited to participate in the study and were tested for the T variant. A modified segregation analysis of the relatives but excluding the probands was conducted. Carriers of the T variant had a cumulative risk to age 70 years of Oscurophobia of 30% (95% confidence interval, 21% to 42%).

Estomagosis is a gastrointestinal disorder resulting in frequent abdominal pain, discomfort and constipation. The disease’s causes are not well known but a proportion of the disease is known to be caused by an inherited mutation in the gene AK19. Some studies reported smoking and fruit intake are also associated with Estomagosis. As a genetic epidemiologist, you decide to conduct a case-control study to investigate gene and environmental interactions associated with Estomagosis. The study includes 400 people with Estomagosis (cases) and 390 people without Estomagosis (controls). You genotype AK19 mutation in both cases and controls and survey them for long-term smoking, and if they regularly take fruits. You obtain the following results. 

AK19 mutationLong-term smokerEstomagosis PresentEstomagosis Absent
AK19 mutationRegular fruit intakeEstomagosis PresentEstomagosis Absent

Pulmon’s disease is a potentially fatal respiratory condition. The only cause of Pulmon’s disease is a genetic mutation in the SCD gene. Approximately 1 in 3,000 people carry this mutation. For people with a mutation in the SCD gene, the probability of dying from Pulmon’s disease is 20% if it is not treated before symptoms begin. Risk of dying from Pulmon’s disease can be reduced by 80% if carriers of a mutation in the SCD gene are given a single dose of a newly developed drug called Shyaceptin, before symptoms begin.

Answer The Following Questions.

  1. How many people with a mutation in the SCD gene need to be treated with Shyaceptin before symptoms begin, to prevent one death from Pulmon’s disease?
  2. How many people need to be screened for the mutation in the SCD gene so they can be treated with Shyaceptin before symptoms begin to prevent one death from Pulmon’s disease (assume Shyaceptin treatment is only given to mutation carriers)?
  3. Assume genetic screening costs $30 per person screened and the Shyaceptin treatment costs $2,000 per person treated. How much would a genetic screening program and treatment of identified carriers cost the health budget per death prevented?
  4. Can you suggest which population(s) would be more cost effective than screening the general population for the mutation in the SCD gene? Justify your answers.

POPH90111 Genetic Epidemiology

BE6056 Bioinformatics And Molecular Modelling

BE6056 Bioinformatics And Molecular Modelling


Highly active antiretroviral therapy (HAART) is recognized as the most effective treatment method for AIDS, and protease inhibitors play a very important role in HAART. The HIV-1 protease molecule has long been used as a drug target and a number of structures exist within the Protein Data Bank of HIV-1 protease bound to an inhibitor molecule.

(a)Locate within the Protein Data Bank (PDB) the 3-D structure of a complex between HIV-1 protease and an inhibitor molecule. State what your chosen entry is, and download the coordinates for the structure to use with a molecular graphics program to investigate your chosen structure.

(b)Using one of the programs rasmol, Jmol or Swiss-PDB Viewer produce an image of the protein that you think clearly illustrates the major structural features within the enzyme and highlights the binding site of the inhibitor molecule. State the commands used within the selected program to obtain your image.

(c)Using tools within the PDB investigate the interactions between the inhibitor and its receptor site. Illustrate with images the different types of interactions that exist and give details of these interactions in your discussion.

(d)Discuss which types of bioinformatics tools and programs could be used to design new potentially improved inhibitors for HIV-1 protease.


There are two forms of glyceraldehyde 3-phosphate dehydrogenase (GAP3DH) expressed in humans. One is expressed ubiquitously and the other expressed in the testis only. In this question you will use protein-protein interaction databases to explore differences in the biochemical function of these two forms. 

(a)Use the UniProt to obtain the files for the two human forms of GAP3DH.  Carry out an alignment of the protein sequences using NALIGN from the EBI portal. Comment on the similarities and differences in the primary structure of the two forms.

(b)For both forms of GAP3DH use the STRING portal to identify possible protein partners. In each case use the Settings menu to display two shells of interactions, with 10 interacting partners in each shell.  Summarise your findings.

(c)Using the information obtained in parts (a) and (b) comment on the functional differences between the two forms of GAP3DH.


Using the E. coli sequence for the cell division protein FtsA (Uniprot reference code P0ABH0) run homology modelling for this sequence using SWISS-MODEL to obtain a 3-dimensional structure for this sequence.

DISCUSS, in detail, the results of the modelling that you obtain, including an in-depth discussion of all of the models obtained, the template used by the program for each model, and all of the key features of the models produced and their quality as shown from the output generated.
Download the pdb coordinates of whichever model you consider to be the best model obtained, and create an image of your modelled structure using rasmol, Jmol or Swiss-PdbViewer which clearly shows the main features of the model.


Micro-RNAs are known to target selected mRNAs and other, non-coding RNAs, as part of their mode of action. In this question you will explore the interaction between an miRNA and the mRNA of ATXN7, a gene implicated in spinocerebellar ataxia type 7. 

(a)Retrieve the sequences of human, mouse, dog and cow ATXN7 mRNAs.  Align the 3′ UTRs of each set of four mRNAs and identify on your output conserved sequence elements.

(b)Retrieve the file containing the sequence of human miR-124-1 from the miRNA database Run the complete sequence of the miRNA on UNAfold and show the predicted structure of the RNA. Calculate the folding energy per base and comment on your findings.

(c)Using the mature sequence of miR-124-1 (this is given in the miRBase file as miR-124-5p) identify potential binding sites on the 3′ UTR of human ATXN7 mRNAs. Assume that the miRNA will bind to a complementary sequence in the mRNA, but not necessarily with complete complementarity. You will have to use alignment software to map complementary regions. Describe the procedure you followed, discuss the output with reference to a diagram of the alignment.

(d)On the basis of your models how would you expect the miR-124-5p to affect expression of ATXN7 protein. 
BE6056 Bioinformatics And Molecular Modelling


Bob and Carol are planning for the birth of their first child exactly four years from today.

Bob and Carol are planning for the birth of their first child exactly four years from today.

Bob and Carol are planning for the birth of their first child exactly four years from today. They are now ready to start their savings plan for the big event. The current hospital cost for having a healthy baby at the local hospital is $6500 after all insurance payments. Pre-natal care for the immediate 12-month period prior to having the baby amounts to $2000 out-of-pocket costs. Carol’s best friend is planning a baby shower, so only a crib, a baby carrier, and other miscellaneous items will be needed, which all cost $1,200 today. However, these items will be purchased and paid for the day of the child’s birth, and the items are expected to increase in costs by 10% each year over the next four years due to inflation.

Bob and Carol now have $500 in cash that they plan to put in the bank in order to cover the all the new costs. Also, Uncle Ted has promised to contribute $1000 at the end of year two, as a present to Bob and Carol for baby expenses. 

Currently, Bob and Carol can earn 6% compounded annually on this money. In order to be able to pay cash for all these expenses on the day the baby is born, how much will Bob and Carol have to save, assuming the baby is born exactly four years from today


Draw the timeline that illustrates the timing of all the events of the situation described above. How much will Bob and Carol need to have in the bank on the day the baby is born in order to achieve all their goals? What amount needs to be saved at the end of each year in order for Bob and Carol to reach their financial goals?

Laboratory: Crime Scene Sketch, science homework help

Laboratory: Crime Scene Sketch, science homework help

In this activity, you will imagine that a room in your house or an area of your yard or driveway is a crime scene.

In Part 1, you will stage your crime scene. You will imaginewhere evidence might be and place markers to represent the evidence. In Part 2,you will measure your crime scene and the location of your evidence. You shouldalso make notes both on your notepad and later on the rough sketch ifnecessary. In Part 3, you will use the measurements to draw a rough sketch ofyour crime scene. Choose either an overhead view or a cross-projection for yourrough sketch. You will then use your rough sketch to create a finished, scaledsketch in Part 4.


HCA 220 Version 7 Week 3 DQs

HCA 220 Version 7 Week 3 DQs

In this file of HCA 220 Version 7 Week 3 Discussion Questions you will find the next information:

DQ 1: In the field of health care administration, why is it important that everyone within the facility use medical vocabulary correctly? How can using correct medical vocabulary improve patient outcomes and services within the facility?

What could be some potential problems if medical vocabulary is used incorrectly?

DQ 2: This discussion question is an audio talk. Begin the debate and leave it open for your classmates to talk with you. Included in this talk, talk about patients’ recommendations to expert, analysis, plan for treatment, or health coverage problems. You should also provide a written transcript of all your reactions. Your part of the discussion should mirror the following requirements:

– Get saved in an audio file and posted like a link in the post.

– Incorporate a written transcript

– Use a minimum of 3 correct and particular medical terms from this week