BIOL207 Lecture 26: b207lect26_1.pdf

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limehippopotamus462

4 Dec 2014

School

University of Alberta

Department

Biology (Biological Sciences)

Course

BIOL207

Professor

Cameron Harrington

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Document Summary

Lecture 26 - human genetic testing: newborn testing for pku, testing for mutant alleles of the brca genes, direct to consumer testing, next-generation dna sequencing, abo blood group, rhesus blood group, newborn testing for pku, biology. Recall that pku is due to the inability to convert excess phenylalanine into tyrosine (lecture 15: guthrie test (1962) Test the newborn"s blood for too much phenylalanine by using it to feed bacteria starved of phenylalanine. Mange and mange, 1999, basic human genetics, 2/e : current testing. Test the newborn"s blood for too much phenylalanine using tandem mass spectrometry proteomics. ucdavis. edu/equipment/tandem-mass-spectrometers-and. Hplcs-lc-msms/10246009 www. health. alberta. ca/professionals/ newborn-metabolic-screening. html: testing for mutant alleles of the brca genes, biology. Mutations in the brca1 and brca2 genes are responsible for 7% of breast cancers. Pongsavee et al. (2009) int j mol sci 10:4187. Analysis consists of sequencing of all translated exons and immediately adjacent intronic regions of the brca1 and brca2 genes and a test for five specific brca1 rearrangements. www. myriadpro. com/treating-diseases/hereditary-cancer-testing/hereditary-breast.

Related Questions

Cystic Fibrosis (CF) is an autosomal recessive genetic disease that is characterized by the secretion of thick, abnormal mucous in the lungs. The mutated gene that leads these symptoms is the CF transmembrane conductance regulator (CFTR gene). The encoded protein is a chloride channel that moves chloride ions out of epithelial cells. In a homozygous individual, the lack of this chloride channel function in a mutant slows the flow of water into extracellular spaces. This lack of water export leads to the heavy mucus in the lungs of CF patients. Although children with CF would die in childhood, current treatments provide life expectancies into the 30âs.

CF is the most frequently inherited genetic disorder among American children. It affects 1 of every 2,500 children; 30,000 currently have the disease. Although its frequency is higher in European populations, it affects all human populations. Heterozygous carrier frequencies in the US are estimated to be 1 out of 29 Caucasians, 1 out of 46 Hispanics, 1 out of 61 African Americans and 1 out of 90 Asians. There are genetic screens for carriers of CF but they are not routinely performed despite this high frequency of carriers. At least all states in the US proscribe testing of newborns to identify children with CF early so that treatment can be started. Newborn tests for CF: http://www.cff.org/AboutCF/Testing/NewbornScreening/ScreeningforCF/ . If CF is such a common genetic disease, and such a simple Mendelian trait, why is genetic screening of parents not done more frequently? Is it just economic, a pain to do, or is it more complex such that the results of genetic testing are not just positive or negative?

Answer the following questions:
1. If two parents are heterozygous carriers of CF, show a pedigree with four children showing the incidence of carriers and afflicted children. If each unafflicted child (carrier or not) mates with another person, who has a 1 out of 30 chance of being a carrier of CF, what is the expected incidence CF disease in the third generation (frequency of CF in any one of grandchildren of the original couple)?

2. Pleiotropy of Cystic Fibrosis. Watch the two videos on the left at:

http://www.cftrscience.com/MOD-animation
or, if you can not view these, read the short NIH Genetics Home Reference for Cystic Fibrosis http://ghr.nlm.nih.gov/condition/cystic-fibrosis

Connect the description with one of the following videos, or related ones (there are many) you see:
video (10 minutes) of daily life of a child with Cystic Fibrosis http://www.youtube.com/watch?v=WUsuGKzdDg8
Lauraâs (20 year old) video diary of life with CF http://www.youtube.com/watch?v=Pgrf8qJXhpc&feature=related

In your own words, describe the range of CF phenotypes. List the other organs besides lungs that are affected and how does it affects those organs.

3.The DNA sequence of the CFTR gene is 170,000 base pairs in length and encodes the CFTR protein that is 1480 amino acids long. Open the accompanying text file (in Canvas/Files/Discussion folder) âCFTR gene DNA sequenceâ. You will see an alignment of the NIH human genome sequence of the CFTR gene â called âReferenceâ rather than âwild-typeâ- against a gene sequence containing a common mutation in CFTR. Look at the alignment and determine how the DNA sequence differs between them. What is the position number where they differ? How many and what nucleotides do they differ in? A â-â mark in one sequence in the alignment means that that base sequence is missing the corresponding bases in the other sequence. The sequence is a long one but the differences are in bolded bright red text. Matching sequence is marked with a | linking the two sequences. Look near the sequence AAATATCATC if you use FIND tool in Word.

In another file, you will an alignment of the reference translated into a protein sequence, compared to the mutant allele translated into protein sequence. The differences are again in red whereas the areas where the proteins match are in black. Look at the alignment. How do these two proteins differ? Again, find the position number and describe how they differ at that location. A â-â mark in the alignment means that amino acid is missing when compared to the other sequence.

4. Given that the CFTR gene can be analyzed for a mutation that causes CF, couples interested in being tested as carriers face several choices given the results.
What could be a consequence of a false positive result (couple is identified as carriers but they would not produce any children with symptoms)?

What could be a consequence of a false negative result (a test indicates the couple is not both carriers but they would produce some children with CF)?

5. The sensitivity of the test can vary with ethnic group. The following is a chart from the NCBI Genetic testing site. A sensitivity less than 100% would be likely to produce false negative results from an inability to determine that someone is carrier.

CF Carrier Test Sensitivity by Ethnic Group http://www.ncbi.nlm.nih.gov/projects/GeneTests/static/concepts/primer/ptscarr5.shtml
Ethnic Group ¹	Population Frequency of CF	Sensitivity of Carrier Detection ²
Caucasian	1 in 29	90%
Ashkenazi Jewish	1 in 29	97%
Native American	1 in 32	94%
Latino	1 in 46	57%
African-American	1 in 60	75%
Asian	1 in 90	30%

Why might different ethnic populations differ in the ability of the genetic test to identify carriers of CF?

Messenger RNA (mRNA)...

a) Is a structural part of a ribosome

b) Brings amino acids to DNA

c) Carries genetic information from the nucleus to the cytoplasm

d) Is a structural part of a chromosome

e) Initiates and directs chemical reactions

Mr. Potato is homozygous dominant (KK), his son, Potato Jr. is heterozygous (Kk). Based on this information, what are the possible genotypes for Mrs. Potato? (Hint: use a Punnet Square).

a) Her genotype is definitely kk

b) Her genotype is either Kk or kk

c) Her genotype is either KK or Kk

d) Her genotype is either KK, or Kk, or kk

e) Mr. Potato cannot be Potato Jrâs biological father

12. Homologous chromosomes:

a) Are members of different chromosome pairs

b) Are genetically identical

c) Carry genetic information that influences the same traits (same genes but probably different alleles)

d) Are only inherited from the mother

e) Are only inherited from the father.

âFitnessâ in an evolutionary sense, refers to an individualâs:

a) Strength

b) Reproductive success

c) Aggressiveness

d) Size

e) Age at death

The fact that individuals who possess favorable traits are more likely to survive and reproduce than those who possess less favorable traits is the basis for the theory of...

a) uniformitarianism.

b) natural selection.

c) the inheritance of acquired characteristics.

d) catastrophism.

e) the fixity of species.

Even with strong selection, genetic variation of a population can be maintained because:

a) Selection only affects one gene at a time.

b) The effects of many alleles are hidden from selection by the effects of other alleles

c) Mutation constantly adds new alleles at an extremely fast rate.

d) Populations always go extinct before their gene frequencies are dramatically altered.

e) Only a and c

Gene Flow is defined as the:
a) Production of new alleles
b) New musical group in which Adam Levine will be the leading vocalist
c) Exchange of genes between populations
d) differential reproductive success of individuals
e) Process by which a DNA base gets extracted out of the nucleus to initiate the process of protein synthesis.

The basic unit of DNA is a molecule called a: a) Nucleotide

b) Base
c) Thymine
d) Prokaryoticcell e) mRNA

How many bases code for one amino acid? a) one

b) two
c) it depends on what amino acid it is d) three
e) four

Hemophilia is a condition that affects: a) more females than males
b) more males than females
c) females and males equally

d) only children born prematurely
e) individuals with a missing portion of chromosome number 5

A clear example of directional selection is:
a) Darwin finches with deeper and thicker beaks associated to a severe drought b) Sickle cell anemia in regions in which Malaria is endemic
c) Achondroplasticdwarfism
d) Fly halteres becoming fully developed wings after modification of a hox gene e) all of the above

Meiosis is evolutionarily significant because:
a) New combination of alleles can arise through independent assortment and crossing over

22.

23.

24.

25.

26.

b) It is the mechanism by which body tissues are repaired
c) It creates somatic cells that are crucial for our body organs to maintain us alive d) It allows forensics to determine the cause of death of unidentified people
e) none of the above

Homologous chromosomes:

a) Are exact copies of each other and contain exactly the same genetic material
b) Are members of different chromosome pairs
c) Are only inherited from the father
d) carry genetic information that influences the same traits (the same genes), however, each of the homologous chromosomes can contain different versions of the same gene (different alleles).

e) carry genetic information that influences different traits because each of the homologous chromosomes contains completely different genes at very different loci

How many chromosome pairs occur in a normal human somatic cell?

a) 46 b) 23 c) 22 d) 24 e) 45

What is the scientific method? Use bullet points to describe the 4 major components.

How is a hypothesis different from a theory?

List the four major components (described during class) necessary for natural selection to occur [AKA Darwinâs Four Postulates] (PDF1-3).

27. Who was Thomas Malthus? In what way(s) Malthus was influential for Darwinâs Theory of Natural Selection? Hint: populations vs resources.

29. What amino acids are being coded for by the gene segment provided below? Nucleotide triplets and their corresponding amino acids are:
ACA= Cysteine; AAA=Phenylalanine; TGG=Threonine; CCT=Glycine; GAT=Leucine; ATA=Tyrosine; AGG=Serine; TCT=Arginine

a) Threonine, serine, glycine, tyrosine, leucine, phenylalanine, arginine, cysteine.

b) Tyrosine, leucine, glycine, threonine, arginine, threonine, serine, cysteine.

c) Arginine, cysteine, serine, glycine, threonine, leucine, phenylalanine, tyrosine.

d) Phenylalanine, leucine, tyrosine, glycine, serine, threonine, cysteine, arginine.

e) Phenylalanine, leucine, tyrosine, glycine, threonine, phenylalanine, arginine, serine.

1. In lecture, we described a simple osmotic pressure gradient when discussing osmosis. For question #1, describe the simple osmotic pressure gradient, in terms of osmotic pressure, that exists across the red blood cell plasma membrane when red blood cells are suspended in a severely hypotonic solution, such as a 0.2% NaCl solution. Use scientific terminology.

2. We mentioned in class that biological systems are always in a state of osmotic equilibrium due to a combination of solute diffusion in some cases and osmosis in others. In this experiment, when you add the red blood cells to a severely hypotonic solution, what substances are moving across the red blood cell plasma membrane to achieve osmotic equilibrium, Na+ and Cl- or water? Explain why based on your understanding of the permeability characteristics of biological membrane. Always use scientific language.

CAN QUESTIONS 1 AND 2 BE ANSWERED DIRECTLY AND ADEQUATLEY PLEASE.

HERE IS AN INTRO TO THE LAB EXPERIMENT

Intro:

We have known for a very long time that the mammalian red blood cell plasma membrane is very permeable to water. Even the introductory biology student understands that if you put mammalian red blood cells in water, they will rapidly swell and break open (hemolyze) due to the rapid osmosis of water into the cell. The experimental question we are asking in today's lab experiment is "Is the high water permability of mammalian red blood cell plasma membrane due solely to the lipid bilayer, or are there water channels present in the membrane?"

Experimental Design:

It has been shown by several investigators that water movement through water channels can be blocked by the known K+ channel blocker, tetraethylammonium chloride (TEAC). Brooks, Regan and Yool (2000) showed that TEAC reduces the water permeability of human water channels expressed in the plasma membranes of frog ocytes. After preincubation of the oocytes for 15 min with 100 microM TEAC, the water permeability of frog oocyte plasma membrane containing human water channels was reduced 20 to 40%. The investigators concluded that treatment of cells with TEAC can be useful in determining the presence of aquaporins in membranes.The specific objective of today's experiment is to uncover the presence of water channels in mammalian red blood cell plasma membrane by determining the effect of tetraethylammonium chloride on the water permeability of mammalian RBC plasma membrane.

BIOL207 Lecture 26: b207lect26_1.pdf

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