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Currently, we are seeing a rare outbreak of measles in the U.S. Although most children are...

Currently, we are seeing a rare outbreak of measles in the U.S. Although most children are vaccinated, this only gives an individual person direct immunity, and then only for their personal lifespan.

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Answer #1

Sex chromosomes are those that carry important information for determining sex.  There are two sex chromosomes in mammals, X and Y.  The X chromosome, which is much larger than the Y, has a centrally-positioned centromere. All other chromosomes are termed autosomes.  Humans have 46 total chromosomes: 44 autosomes and 2 sex chromosomes.  Or, 22 pairs (homologous chromosomes) of autosomes and 1 pair of sexchromosomes.  The sex chromosomes are homologous to one another.

    Normal females have two XX chromosomes, normal males have an X and Y chromosome.  Nettie Sloan first discovered this is 1900.  Thus, after meiosis, all female eggs will have one X chromosome, whereas, 50% of sperms will carry the X chromosome and 50% the Y chromosome (see diagram in class). When sperm and egg recombine, there is a 50% chance of having a female, and 50% chance of having a male. We can set up a Punnet square to represent this situation.   

X X
X XX XX
Y XY XY

    Thus, there is 1:1 ratio of male to female offspring or 1 in 2 (1/2) chance of having a boy or girl or 50% chance of having a girl or boy.  In practice slightly more males are conceived, possibly because the Y carrying sperm swim faster.

    Folk tales state that the male determines the sex of the child.  This is true only in the sense that sperms come in two "flavors" (X and Y), whereas eggs in only one (X).  Thus, depending upon which sperm fertilizes the egg, that will determine the sex of the offspring.


III.  Nondisjunctions
     Non-disjunction at meiosis (or mitosis) is one cause of unusual combinations of chromosomes (a cell/individual with odd numbers of chromosomes is termed aneuploid).  Nondisjunction is the failure of chromosomes to properly segregate during meiosis.  In other words, it is a violation of the Law of Segregation.  Nondisjunction can occur at meiosis I or II.  (see diagrams).

    Common aneuploids include:  XXX - triple X syndrome, female, 47; XXY - Kleinfelters syndrome, male, 47, (frequency about 1 in 1000 live births); XYY - male, 47; XO - Turner's syndrome, female, 45 (about 1 in 5000 live births); Down's syndrome (trisomy 21; frequency increases with maternal age).  

    Cells can tolerate imbalances of sex chromosomes better than imbalances of autosomes.  With the exception of Down's syndrome and a couple of others like Edwards syndrome (trisomy 18) or Patau's (trisomy 13), there are few live births of autosomal aneuploids and individuals are severely afflicted. Why are cells able to tolerate extra sex chromsomes? Because....

  1. Extra X chromosomes are inactivated so they don't "mess things up".  Mary Lyon first observed that in normal females only one X chromosome remains active, any additional ones are inactivated during development (after about 10 embryonic divisions).  The inactivated X chromosome forms a small dark staining spot in nucleus, called a Barr body.  This forms the basis for the sex test.  Thus, only one remains active, the others inactivate as Barr bodies.  Barr body number:  XX - 1 Barr body; XXX - 2 barr bodies; XXY - 1 Barr body; XYY - no Barr body; XY - no Barr body. (Note:  the chromosome that is inactivated is at random.); and

  2. Y chromosomes are small and carry comparatively little genetic information that will "mess things up".


IV.  Karyotypes
    A karyotype is used to determine the chromosome composition of an individual. White blood cells are typically used (red cells lack a nucleus), they are treated with colchicine which prevents the formation of microtubules.  Thus, cell division stops at metaphase, allowing a good view of the spread chromosomes.  The chromosomes are stained, photographed and arranged from large to small, matching homologs (see exercise).  

    Some parents want to know if the offspring they are carrying is "normal."  Amniocentesis (removal of amniotic fluid containing fetal cells is obtained) or chorionic villi biopsy (remove some of fringe around embryo) permit sampling of fetal tissue to determine karyotype and other genetic conditions.

V.  Sex-Linked Genes

A. Coat color in cats: X-linked trait.
    Let's talk about cats, specifically calico cats which are orange, black and white.  The coat color gene is carried on the X chromosome.  Thus this gene is called X-linked (or sex-linked for a more general term).  There aretwo forms of expression (called alleles) for this trait - XO and XB.  The XO allele codes for orange pigmentation and the XB for black spots.  If both alleles of a pair are the same, we call it homozygous; if they are different,heterozygous. Thus, in a diploid cell there are three possible combinations of alleles:  XO XO, XO XB, and XB XB.  Cats with these combinations appear:  white with orange spots, white with black and orange spots (calico), and white with black spots, respectively. The actual genetic composition is called the genotype, and the expression of the genes is the phenotype.  Thus, calico is the phenotype for a cat with the genotype XO XB.

    Note that so far we have only considered female cats.  Male cats can have the genotype XB Y  or XOY.  The phenotype of the first would be white with black spots, the second will have orange spots.  Thus, all calico cats are female!  (there is the rare sterile male with the genotype XO XB Y).

    As an aside, recall that the X chromosome that becomes inactive as a barr body does so randomly. This explains why calico cats have random splotches of black or orange, depending upon which chromosome carrying which allele was inactivated in the cell line that gave rise to that part of the cat. Also note that these alleles are codominant; that is, both are expressed in the heterozygote.  In many cases, one allele (dominant) dominates over the expression of the other (recessive).  Thus, heterozygotes will express the dominant trait.  

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Answer #2

All UC Berkeley mumps patients had two vaccinations

Hundreds of UC Berkeley students and employees lined up outside the campus health center Thursday for free vaccinations after a mumps outbreak infected up to 20 students.

A spokeswoman for the health center said the university and state public-health officials expected to vaccinate more than 1,000 people by the time the clinic closed at 6 p.m. The university will hold another free clinic from noon to 6 p.m. Oct. 14.

The state Department of Public Health was monitoring the rare outbreak this week. A department spokesman said he had no update on the number of students infected. Seven cases had been confirmed and 13 other students were being tested.

Although health officials initially wondered whether the outbreak started with students who had not been vaccinated, a spokeswoman for the city of Berkeley said all the patients had received the two recommended doses before becoming ill.

Source: Contra-Costa Times, 7th October 2011.

VAN UK's Comment: That makes sense, they're already vaccinated, an outbreak happens so they line up to get vaccinated??

Vaccine-Derived Poliomyelitis 12 Years after Infection

DeVries et al. (June 16 issue)1 describe a patient with vaccine-derived poliomyelitis. We were unable to clear chronic, asymptomatic, neurovirulent poliovirus infection in a similarly antibody-deficient patient despite the use of antiviral therapy, breast milk, and oral immune globulin.2 In our patient, the mean IgG trough levels were 1000 mg per deciliter, and paralysis did not develop during an estimated 29 years of poliovirus infection. Neutralizing antibodies against his own poliovirus isolates were detected in his replacement immune globulin by the National Institute for Biological Standards and Control.3 In the patient described by DeVries et al., the IgG trough levels were 438 and 648 mg per deciliter before the onset of paralysis, and the immune globulin

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Answer #3

Sex chromosomes are those that carry important information for determining sex.  There are two sex chromosomes in mammals, X and Y.  The X chromosome, which is much larger than the Y, has a centrally-positioned centromere. All other chromosomes are termed autosomes.  Humans have 46 total chromosomes: 44 autosomes and 2 sex chromosomes.  Or, 22 pairs (homologous chromosomes) of autosomes and 1 pair of sexchromosomes.  The sex chromosomes are homologous to one another.

    Normal females have two XX chromosomes, normal males have an X and Y chromosome.  Nettie Sloan first discovered this is 1900.  Thus, after meiosis, all female eggs will have one X chromosome, whereas, 50% of sperms will carry the X chromosome and 50% the Y chromosome (see diagram in class). When sperm and egg recombine, there is a 50% chance of having a female, and 50% chance of having a male. We can set up a Punnet square to represent this situation.   

X X
X XX XX
Y XY XY

    Thus, there is 1:1 ratio of male to female offspring or 1 in 2 (1/2) chance of having a boy or girl or 50% chance of having a girl or boy.  In practice slightly more males are conceived, possibly because the Y carrying sperm swim faster.

    Folk tales state that the male determines the sex of the child.  This is true only in the sense that sperms come in two "flavors" (X and Y), whereas eggs in only one (X).  Thus, depending upon which sperm fertilizes the egg, that will determine the sex of the offspring.


III.  Nondisjunctions
     Non-disjunction at meiosis (or mitosis) is one cause of unusual combinations of chromosomes (a cell/individual with odd numbers of chromosomes is termed aneuploid).  Nondisjunction is the failure of chromosomes to properly segregate during meiosis.  In other words, it is a violation of the Law of Segregation.  Nondisjunction can occur at meiosis I or II.  (see diagrams).

    Common aneuploids include:  XXX - triple X syndrome, female, 47; XXY - Kleinfelters syndrome, male, 47, (frequency about 1 in 1000 live births); XYY - male, 47; XO - Turner's syndrome, female, 45 (about 1 in 5000 live births); Down's syndrome (trisomy 21; frequency increases with maternal age).  

    Cells can tolerate imbalances of sex chromosomes better than imbalances of autosomes.  With the exception of Down's syndrome and a couple of others like Edwards syndrome (trisomy 18) or Patau's (trisomy 13), there are few live births of autosomal aneuploids and individuals are severely afflicted. Why are cells able to tolerate extra sex chromsomes? Because....

  1. Extra X chromosomes are inactivated so they don't "mess things up".  Mary Lyon first observed that in normal females only one X chromosome remains active, any additional ones are inactivated during development (after about 10 embryonic divisions).  The inactivated X chromosome forms a small dark staining spot in nucleus, called a Barr body.  This forms the basis for the sex test.  Thus, only one remains active, the others inactivate as Barr bodies.  Barr body number:  XX - 1 Barr body; XXX - 2 barr bodies; XXY - 1 Barr body; XYY - no Barr body; XY - no Barr body. (Note:  the chromosome that is inactivated is at random.); and

  2. Y chromosomes are small and carry comparatively little genetic information that will "mess things up".


IV.  Karyotypes
    A karyotype is used to determine the chromosome composition of an individual. White blood cells are typically used (red cells lack a nucleus), they are treated with colchicine which prevents the formation of microtubules.  Thus, cell division stops at metaphase, allowing a good view of the spread chromosomes.  The chromosomes are stained, photographed and arranged from large to small, matching homologs (see exercise).  

    Some parents want to know if the offspring they are carrying is "normal."  Amniocentesis (removal of amniotic fluid containing fetal cells is obtained) or chorionic villi biopsy (remove some of fringe around embryo) permit sampling of fetal tissue to determine karyotype and other genetic conditions.

V.  Sex-Linked Genes

A. Coat color in cats: X-linked trait.
    Let's talk about cats, specifically calico cats which are orange, black and white.  The coat color gene is carried on the X chromosome.  Thus this gene is called X-linked (or sex-linked for a more general term).  There aretwo forms of expression (called alleles) for this trait - XO and XB.  The XO allele codes for orange pigmentation and the XB for black spots.  If both alleles of a pair are the same, we call it homozygous; if they are different,heterozygous. Thus, in a diploid cell there are three possible combinations of alleles:  XO XO, XO XB, and XB XB.  Cats with these combinations appear:  white with orange spots, white with black and orange spots (calico), and white with black spots, respectively. The actual genetic composition is called the genotype, and the expression of the genes is the phenotype.  Thus, calico is the phenotype for a cat with the genotype XO XB.

    Note that so far we have only considered female cats.  Male cats can have the genotype XB Y  or XOY.  The phenotype of the first would be white with black spots, the second will have orange spots.  Thus, all calico cats are female!  (there is the rare sterile male with the genotype XO XB Y).

    As an aside, recall that the X chromosome that becomes inactive as a barr body does so randomly. This explains why calico cats have random splotches of black or orange, depending upon which chromosome carrying which allele was inactivated in the cell line that gave rise to that part of the cat. Also note that these alleles arecodominant; that is, both are expressed in the heterozygote.  In many cases, one allele (dominant) dominates over the expression of the other (recessive).  Thus, heterozygotes will express the dominant trait.

IX.  Lessons From a Monk:  Gregor Mendel
    Called the "Father" of genetics.  Normally, I would use gender-inclusive language and call such a person the "Founder" of Genetics.  In this case, "Father" is correct because Mendel was monk in the monastery of St Thomas, Brunn (now Brno) near Vienna.  He was born in 1822.  He published the first work on genetics in 1865 called "On the Nature of Inheritance".  He studied the inheritance of traits in peas.

    Peas were a terrific choice because:  

  1. there were lots of hybrids that had previously been studied;

  2. there were true breeding varieties available (i.e., when allowed to self pollinate or mated with another individual of the same type, they produced more of the same variety);

  3. they are small, easy to grow and have a reasonably short life cycle;

  4. the flowers are good for breeding studies (readily self pollinate, easy to remove stamens for cross pollination studies).

    Mendel's work was ignored for 35 years, when it was simultaneously "discovered" by three botanists (Tschermak, Correns, de Vries).  It was ignored because it was:  

  1. too sophisticated using brilliant, carefully controlled experiments (he was a man ahead of his times);

  2. too much math/stats for people to understand;

  3. published in an obscure journal;

  4. Mendel was not in the scientific mainstream; and

  5. he stated his ideas poorly (a good reason to do well in Symposium!).

    Mendel studied 7 different traits (genes) each with two forms of expression (alleles)  These are

  • seed texture - smooth, wrinkled

  • flower position - axillary, terminal;

  • pod form - inflated, constricted

  • stem length - tall, dwarf

  • seed color - yellow, green

  • flower color - red, white

  • pod color - green, yellow

    These genes are located on 4 of the 7 pairs of homologous chromsomes (2n=14).  Flower color and seed color are on chromosome 1; flower position, pod shape, and plant height are on chromosome 4; pod color on chromosome 5; and seed shape on chromosome 7.

So, what were Mendel's actual contributions? He determined:  

  1. Hereditary information is transmitted in particles or units (that we now call genes).  [A gene specifies a particular trait or feature of an individual. The phenotype is the outward expression of the genes and the genotype refers to the specific genetic makeup that translates into the phenotype];

  2. There are two factors (allele) for every trait in a diploid individual (on homologous chromosomes) [An allele is the form of expression of a gene];

  3. The two alleles may be the same (homozygous) or different (heterozygous);

  4. Alleles don't blend their expression, like mixing a can of paint. This seems obvious now, but the dominant paradigm of the day was that alleles blended.  For example cross a red flower with a white flower to get pink which becomes would become diluted more and more in subsequent crosses.  In contrast, if alleles are discrete, then mix red and white and get pink, but mix pink and pink and you could get back red and white;

  5. One unit from every pair moves into gametes during meiosis (Law of Segregation).  In other words, homologous chromosomes separate during meiosis;

  6. The expression of one allele (dominant) usually predominates over the other (recessive);

  7. Genes act independently of one another (i.e, Law of Independent Assortment, homologous chromosomes separate randomly in meiosis).

X. Multiple Alleles.  
    This is the situation where there are more than two alleles at a locus responsible for a particular trait.  (versus two alleles for all the traits that we have discussed so far).  A good example is the ABO blood groups in humans.   

    Three alleles are responsible for ABO blood type.  These are:  

  • IA - this allele codes for A antigens on the cell surface of the red blood cells (an antigen is a substance that stimulates the production of an antibody. Specifically, this gene causes galactosamines to be attached to lipids on the cell surface);  

  • IB - specifies B antigens on rbc (adds galactose to cell surface lipids; and

  • i (or O) -  no antigens on cell surface.

    Thus, an individual can have the following phenotypes/genotypes:

Blood type Genotype (s) Antigen on RBC surface Antibodies in plasma
A IAIA , IA i A antibodies against B (anti B)
B IBIB, IB i B antibodies against A (anti A)
AB IAIB A and B none (= universal recipient)
O ii none (= universal donor) anti A and anti B

Note:  These alleles are codominant (one does NOT dominant over the expression of the other).  In other words, in the heterozygote, both are expressed in the phenotype.  As an aside, if you have type A blood, you have antibodies against type B antigens.  Antibodies react with the antigens that stimulated its production to remove it from the body.  Individuals with type B blood have antibodies against type A antigens, type O blood has antigens against both A and B antigens and individuals with AB blood have no antibodies.  Thus, type O blood is the universal donor (since it has no antigens on rbc, it won't be attacked by either antibody) and type AB is the universal recipient (because it has no antibodies, won't react with either A or B antigens).

Genetics of blood types:  Crosses work just like others described above.  For example:    

  1. Consider a mother with type AB blood and a father with type AB.  What progeny and in what proportions do you expect?  Answer:  1/4 type A, 1/4 type B, 1/2 type AB.

  2. Consider two parents, one type A and the other type B.  Can they have a child with type A blood?  type B?  type AB?  type O?  Answers:  It depends on the actual genotypes of the parents.   

  3. Consider a family in which the father has type B blood, the child type A blood and the mother type O blood.  Dad says he's not the father of the child.  What do you conclude?  Answer:  Dad is right.  Since we know the mother of the child has type O blood the child must have at least one "i" allele.  Thus, the other allele is "A".  Since the father is type B, he could not have contributed the A allele, and therefore, is not the father. Note:  blood genetics can confirm a person is NOT a parent, but cannot prove that a person IS the parent

Rh Antigens
    These are another type of antigen found on red blood cells.  They were first recognized in rhesus monkeys, hence the abbreviation.  Either your rbc cells have the antigens (RH+) or not (Rh-).  Rh positive individuals never produce antibodies against Rh antigens.  Rh negative individuals don't normally produce antigens but can be induced to do so if exposed to Rh+ blood (as might happen in a transfusion, which is unlikely in modern medicine, or it could easily happen if an Rh- mom gives birth to an Rh+ child).  In the latter case, the mother is given a shot of rhogam soon after delivery to scavenge up the Rh+ antigens to prevent her immune system from producing Rh antibodies that might affect subsequent children.  

Hair Color
    This is another example of a trait coded by multiple alleles and by two genes. One gene with two alleles (R+, R-) codes for the production of red pigment and a second gene with multiple alleles codes for the amount of pigment deposited in the hair (bd - blonde, light deposition; Bw - brown, medium deposition; Bk - black, heavy deposition). As a result, a large number of hair colors, from strawberry blonde to glossy black, possible.

XI. Incomplete Dominance & Summary/Review of relationships between alleles
        Incomplete dominance is the situation in which neither allele dominates over the expression of the other.  Rather, the heterozygote shows an intermediate expression of the phenotype.  The classic example is flower color in snap dragons.  Two alleles are responsible for flower color, R - red and R' - allele.  Thus, there are three genotypes/phenotypes:  RR - red flowers, RR' - pink flowers, and R'R' - white flowers.

    A cross between two pink flowering plants will yield an expected phenotypic ratio of 1:2:1, or in other words, 1/4 are expected to be red, 1/4 white and 1/2 pink.  The 1:2:1 ratio should be a good clue that you are dealing with incomplete dominance.  

Summary of allelic relationships:  

If in the heterozygote....

  • one allele is expressed, then it's said to be dominant

  • both alleles are expressed, then it's said to be codominant

  • neither allele is expressed but appears blended, then it is said to be incomplete dominance


XII.  Gene Linkage
    Linked genes are those that are found on the same pair of homologous chromosome.  Earlier we discussed sex linkage which refers to genes found on the X (or Y) chromosome.  Thus, their inheritance is linked with sex. Obviously, countless autosomal genes are linked. If you assume that humans have about 50,000 genes (Human Genome Project) and since there are 23 pairs of homologous chromosomes, on average, there must be about 2000 genes per chromosome (50,000/23).  Those that are found on the same pair of homologous chromosomes are linked.

    Let's return to Mendel's work with peas to provide some examples: The seed texture gene and the seed color genes are not linked because they occur on different chromosomes - seed texture is on chromosome #7 and seed color on chromosome #1. The genes for flower color and seed color are linked - they are both carried on chromosome #1. How about the genes for pod shape and stem height; are they linked?


XIII.  Dihydrid Crosses.  
    Individuals that differ in two traits.  In class, we will go through a worksheet together examining a cross in peas.  Points to note:  (a) dihybrid crosses involved two genes, each usually with two alleles; (b) if the genes are not linked, then a completely heterozygous individual can produce four types of gametes; (c) a mating between two completely heterozygous individuals results in 4 types of offspring, in a ratio of 9:3:3:1.  In other words, 9/16 show the two dominant traits, 1/16 show the two recessive traits, 3/16 are recessive for one trait and dominant for the other, and the other 3/16 show the same thing only reversed; (d) a mating between a heterozygous individual and homozygous recessive results in a ratio of 1:1:1:1 ratio; and (e) linkage results in unexpected ratios of offspring.

     A fun example from a bird lover:  Color in parakeets (budgies, which is short for budgerigars).  Two genes that are not linked are responsible for feather color.  One gene codes for the production of a melanin in the center of the shaft (B = blue/black; b = no blue black 'cuz no melanin in center of shaft).  The other gene codes for a yellow pigment in the other part of the feather (Y = yellow pigment, y = no yellow).  Thus four phenotypesare possible: Green birds (B_Y_); blue (B_yy); Yellow (bbY_); and white (bbyy).

Example:  Consider a cross between a heterozygous green bird and a white one.  What offspring and in what frequency do you expect?  Answer: 1/4 green; 1/4 blue; 1/4 yellow; 1/4 white.


XIV.  Crossing Over.  
    The exchange of portions of chromatids during meiosis will result in new combinations of alleles in chromosomes.  See worksheet in class.  Take home lesson:  recombinant gametes/offspring are those that are the product of a crossing over and usually occur in low frequency.  The frequency of crossing over is related to the distance the genes are separated on the chromosome.  That is, the further apart the two loci are, the greater the probability that crossing over will occur between the two.


XV.  Pleiotropy.  
    Situation where a single gene affects many traits.  In other words, a one gene has many different effects. (note this is in contrast to situations were have discussed above where one gene affects one trait).

     A good example is Marfan's Syndrome, also called Abe Lincoln disease.  This is caused by a dominant allele and it results in the production of abnormal connective tissue.  Afflicted individuals have skeletal problems (long limbs, loose joints), cardiovascular problems and eye defects.  Lincoln was described as tall and lanky. There is some evidence he was not well during the last years of his life and may have been afflicted with this disease.  Some think he may have died from it had he not been assassinated.


XVI.  Polygenic Inheritance.  
    This is where a single trait is influenced by many genes.  It is common, especially in traits that exhibit continuous variation (no clear cut differences) such as height, eye color or skin color.       

     For example, there are at least three genes involved in eye color.  One gene codes for melanin production (yes = normal, dominant allele, no = albino, recessive). A second gene determines whether melanin is deposited in the outer layer of the iris of the eye (yes = some shade of brown, dominant; no = blue).  The third gene(s) determines the density or amount of melanin deposited in the iris.  Thus, eye color is the result of production, distribution and concentration of melanin in the eye.  If no melanin, then the eye appears red, from the blood vessels at the back of the eye.  If melanin is produced, it is placed in the retina.  The eye will appear blue as lightreflects off the retina.  Melanin deposited in the iris will result in a shade of brown.


XVII.  Epistasis.  
    This is the situation where one gene influences the expression of another.  In other words, genes interact with one another.  Eye color is one good example.  If there is no melanin producing gene, then the other genes cannot be expressed.

    Sweet pea flower color.  Note this trait is coded for by two genes that aren't linked.  Assume that you cross purple (PPCC) and white (ppcc) flowering plants.  The F1 will all be PpCc or purple flowering.  A cross between two heterzygotes will result in an F2 ratio of 9:7 (purple to white).  The purple trait will only be expressed if both genes have dominant alleles.  The reason is because the pigment is made by a multistep pathway, similar to the production of adenine yeast.  Thus   A

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Answer #4

U.S. Although most children are vaccinated

Well, its not like we didn

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