Meiosis – Chromosomal Disjunction

In eukaryotic organisms, gametes (eggs, sperm) form via meiosis, a process of cellular
division resulting in the production of four haploid (1N) daughter cells from a single
diploid (2N) parental cell.  Meiosis occurs in two stages, meiosis I and meiosis II, each of
which is composed of prophase, metaphase, anaphase, and telophase followed by
cytokinesis (cell division):

1. Meiosis I:  In prophase I, the nuclear envelope of a diploid parental cell

disintegrates and homologous chromosomes (each consisting of two sister
 chromatids) pair up.  In the phase that follows (metaphase I), these chromosomes
align in the middle of the cell (ie, at the metaphase plate).  The chromosomes are
pulled to opposite poles of the cell by the meiotic spindle in anaphase I.  The
nuclear envelope then reforms in telophase I and the cytoplasm of the cell divides
(cytokinesis) to yield two haploid daughter cells.
2. Meiosis II:  A process similar to meiosis I occurs in this stage, with the exception
that it occurs in the previously formed haploid daughter cells.  Following nuclear
envelope disintegration in prophase II, chromosomes align at the metaphase plate
during metaphase II.  However, in anaphase II sister chromatids (not homologous
chromosomes) are pulled to opposite poles of the cell by the meiotic spindle. 
Reformation of the nuclear envelope in telophase II and cell division (cytokinesis)
of each cell yields four haploid daughter cells.

If a diploid cell with 46 chromosomes undergoes meiosis, four haploid daughter cells
should be produced with each containing 23 chromosomes.  However, in the given scenario
two daughter cells have an extra chromosome and two daughter cells are missing a
chromosome.  Such a finding is most likely due to chromosomal nondisjunction, which
occurs when either homologous chromosomes (during anaphase of meiosis I) or sister
chromatids (during anaphase of meiosis II) fail to separate to opposite poles of the cell. 
Chromosomal nondisjunction during anaphase I may produce one daughter cell with an
extra homologous chromosome (24 chromosomes) and one daughter cell missing a
chromosome (22 chromosomes) (Choices A, B, and C).  Division of these cells in meiosis
II would yield two cells with 22 chromosomes and two cells with 24 chromosomes.

Educational objective:
During meiosis, chromosomal nondisjunction occurs when homologous chromosomes (in
meiosis I) or sister chromatids (in meiosis II) fail to separate to opposite poles of the cell
during anaphase, leading to extra chromosomes in some daughter cells and missing
chromosomes in others.

Incomplete dominance and codominance – Genetics

Individuals heterozygous for a trait possess two distinct alleles (ie, versions) for the gene
encoding that trait.  However, the way that these distinct alleles interact to give rise to
specific traits in a heterozygous individual may vary.  In some heterozygotes, a completely
dominant allele in one copy of the gene phenotypically masks a recessive allele in the other
copy of the gene.  In other cases, however, both alleles may be phenotypically expressed,
producing heterozygous individuals with combined or blended traits.

Specifically, incomplete dominance between alleles results in a blended or intermediate

phenotype in heterozygous individuals.  A common example of incomplete dominance is a
cross between homozygous red flowers (RR) and homozygous white flowers (WW)
producing heterozygous offspring (RW) that are pink.

In the given scenario, a gene regulating tail length in bobtail cats has two alleles at the same
locus: an allele producing long tails (L) and an allele producing short tails (l).  Mating a
male cat homozygous for short tail length (ll) with a female cat homozygous for long tail
length (LL) produces heterozygous offspring (Ll) possessing both alleles.  The graph
shows that these heterozygous offspring have longer tails than the father's but shorter tails
than the mother's, meaning that these offspring have an intermediate phenotype
compared with their parents.  This observation supports the conclusion that these alleles for
tail length exhibit incomplete dominance because incomplete dominance of alleles in
heterozygous individuals results in intermediate phenotypes.

(Choices A and B)  Although heterozygotes inherit both types of alleles, only observations
of phenotypic traits in these individuals inform scientists of whether the alleles exhibit
incomplete dominance or another mechanism of inheritance (eg, completely
dominant/recessive inheritance, codominance).  In addition, although all heterozygous
offspring have longer tails than their father's, they all also have shorter tails than their
mother's, and this observation supports the conclusion that the alleles influencing tail length
in these cats exhibit incomplete dominance.

(Choice C)  Although the tail lengths between offspring do vary, this observation alone
indicates variable expressivity (not incomplete dominance) of the phenotype. 
Determination of whether the alleles regulating tail length show incomplete dominance
requires that the tail lengths of the offspring be compared with those of the parents.

Educational objective:
Incomplete dominance between alleles results in the expression of phenotypes in
heterozygous offspring that are intermediate to the phenotypes of homozygous parents.
Immune system – self tolerance

Normally, the immune system is said to be self-tolerant because it does not attack itself
but serves to protect the body from foreign substances (antigens).  During the early stages
of immune cell development, which occurs in the thymus (T cells) and bone marrow (B
cells), cells undergo genetic recombination to rearrange their DNA.  This rearrangement
leads to the expression of novel antigen-binding receptors and antibodies on the surface of
T cells and B cells, respectively.  The production of billions of immune cells with varied
receptor sets results in an immune system able to target many different antigens.  However,
the rearrangement also results in the expression of receptors that target endogenous
molecules (self-antigens).  To avoid rampant immune responses against self, these self-
recognizing cells are normally destroyed.

Negative selection is the process by which immature T cells and B cells possessing
receptors that bind to self-antigens are destroyed.  Elimination of these cells occurs either
by programmed cell death (apoptosis) or by becoming unresponsive to antigens (anergic). 
According to the question, rheumatoid factor (RF) is an antibody that mediates an
autoimmune response by targeting a patient's own IgG antibodies.  RF is not usually made
in high concentrations because B cells and T cells that mediate self-recognition and
antibody production are typically destroyed during negative selection.

(Choice A)  Complement proteins are blood proteins that increase the effectiveness of
antibodies by helping to recruit and activate phagocytes.  The question describes RF as an
antibody that targets self-IgG antibodies; it is not a complement protein.

(Choices C and D)  Rearrangement of DNA leads to the expression of surface

antibodies/receptors that can identify self-antigens (B cells and T cells).  Identification of
self-antigens by B cells enables subsequent presentation of the self-antigens.  However,
these self-recognizing cells are normally destroyed during immune cell maturation.

Educational objective:
Autoimmunity disorders occur due to the immune system's failure to identify and destroy
immune cells that recognize self-antigens.  Self-reactive B cells and T cells are normally
eliminated in the bone marrow and thymus, respectively.

Loop of henle – glomerular filtration rate

Each kidney, divided into an outer cortex and inner "salty" medulla, contains many
functional units known as nephrons.  In the renal cortex, blood is first filtered through
glomerular capillaries into the Bowman's capsule (a cup-shaped structure) of each nephron. 
The filtered fluid (filtrate) then flows through the tubular segments of the nephron.  The
proximal tubule is the first segment the filtrate traverses.  Next, the filtrate flows into the
loop of Henle, a two-limbed structure stretching into the medulla that reabsorbs water and
salt (NaCl) from the filtrate into the body via countercurrent multiplication:

1. Filtrate flows through the descending limb of the loop, which is highly permeable to
water but impermeable to NaCl.  Water will move from areas of low solute
concentration to areas of high solute concentration.  Accordingly, because salt
concentration in the medulla is high, water is passively reabsorbed (via osmosis)
from the filtrate flowing through the descending limb into the salty medulla, where
it is taken up by blood vessels.
2. Filtrate then flows into the ascending limb, which is highly permeable to NaCl but
impermeable to water.  Initially, NaCl is passively reabsorbed into the medulla as
filtrate moves up the ascending limb.  However, as the ascending limb nears the
cortex, NaCl is actively transported from the filtrate into the medulla, preserving the
medulla's high salt concentration.  Because water follows NaCl, the saltiness of the
medulla promotes continued water reabsorption from the descending loop of Henle
and the collecting duct.

Following passage through the loop of Henle, filtrate travels through the distal tubule into
the collecting duct, where water and salt reabsorption continue.  Remaining filtrate flows to
the bladder and is excreted from the body as urine.

Studies in mice indicate that sodium transporter mutations impair active transport of
NaCl from the loop of Henle into the medulla.  Accordingly, compared to wild-type mice,
mice with mutated sodium transporters would exhibit a decrease in both medullary salt
concentration and water reabsorption (Choices A and C), a decrease in blood pressure
(Choice D), and an increase in urine output (Choice B).

Educational objective:
In the loop of Henle, active transport of NaCl from filtrate in the ascending limb maintains
the saltiness of the renal medulla, facilitating passive water reabsorption from filtrate in the
descending limb and collecting duct.
Gene Expression selectivity
An organism's genome comprises the complete set of genes possessed by that organism,
and the expression of these genes produces proteins that confer various traits (ie,
phenotypes) to the organism.  However, certain environmental conditions (eg, temperature,
diet, oxygen level) may influence gene expression or alter protein function, affecting an
organism's phenotype.  This relationship between an organism's genetic make-up and the
environment is known as a gene-environment interaction.

In this scenario, certain turtles experience temperature-dependent sex determination.  This

is an example of a gene-environment interaction during a developmental process.  Unlike
humans, the sex of the developing embryos for these turtles is determined by the
temperature at which the egg is incubated, not by the presence or absence of specific sex
chromosomes.

The turtles express an enzyme during embryonic development that converts male sex
hormones (ie, testosterone) to female sex hormones (ie, estrogen).  This enzyme's
expression level (and corresponding amounts of male or female sex hormones) determines
whether an embryo develops as male or female.  Accordingly, high expression of this
enzyme in embryos increases the conversion of male to female sex hormones, increasing
the presence of female hormones and inducing female development.  In contrast, low
expression of this enzyme decreases the conversion of male to female sex hormones,
increasing the presence of male hormones and inducing male development.

The scientists hypothesized that expression of this enzyme in turtle embryos depended on
incubation temperature.  To test this, they incubated groups of turtle eggs at either 26°C or
30°C and recorded the sex of each turtle after hatching.  The graph shows that most
embryos in eggs incubated at 26°C developed as male, signifying that enzyme levels
would be low at 26°C because reduced expression of this enzyme promotes male
development.  In contrast, the graph shows that most embryos in eggs incubated at 30°C
developed as female, meaning that enzyme levels would be high at 30°C because
elevated enzyme levels promote female development (Choices A, C, and D).

Educational objective:
In general, the expression of genes produces proteins, and the properties and activities of
these proteins lead to the expression of certain traits (phenotypes) in organisms.  However,
in a gene-environment interaction, certain environmental conditions (eg, temperature, diet,
oxygen level) can influence gene expression or protein activity and alter an organism's
phenotype.
Drainage from circulatory system to the lymphatic system, and back into
the bloodstream
When blood flows through capillaries, some fluid containing plasma proteins leaks out of
the blood vessels and into the interstitial fluid.  The interstitial fluid fills the space between
blood vessels and surrounding cells.  Leaked excess fluid from the capillaries, now also
known as interstitial fluid, must be returned to the bloodstream to maintain the proper blood
volume and protein concentration.  To reenter the bloodstream, the fluid must first pass
from the interstitial space and enter a network of vessels and nodes known as the lymphatic
system.  Once in the lymphatic system, this fluid is now known as lymph and is ultimately
drained into two large veins near the heart.

In addition, the lymphatic system also collects large lipid droplets absorbed by the small
intestine.  Certain lipids digested in the small intestine are absorbed by intestinal epithelial
cells and packaged into large droplets.  However, their large size prevents them from
crossing directly into the capillaries surrounding intestinal cells.  Instead, these lipid
droplets are transported through the lymphatic system and into the bloodstream as follows:

1. Lipid droplets are released from the epithelial cells into the interstitial fluid.
2. Lymph capillaries collect lipid droplets from the interstitial fluid.
3. Lymph containing the lipid droplets then flows from the capillaries into increasingly
larger lymph vessels.
4. Lymph is then transported into a large tubule structure called a lymph duct, which
drains into a large vein near the heart.  As a result, the lipid droplets within the
lymph enter the bloodstream and circulate throughout the body (Choices A, B, and
D).

Educational objective:
The lymphatic system collects protein-containing fluid leaked from blood capillaries and
transports it back to the bloodstream.  In addition, large lipid droplets absorbed by the small
intestine are also transported to the bloodstream via lymph vessels.  Fluid is collected by
lymph capillaries, flows into larger lymph vessels, and is transported into lymph ducts that
drain into veins near the heart.

Spermatogenesis and oogenesis

Spermatogenesis (males ♂) Oogenesis (females ♀)
Start of process Puberty Prior to birth (in fetal stage)
Never, spermatogenesis Stops at menopause (cessation
End of process
continues throughout life of menstruation)
Gonads (site
Testes Ovaries
of production)
Timing of gamete
production Continuous Monthly
& release
Occur without interruption &
Arrested at certain stages
Meiotic cell produce similarly-sized
& produce cells of unequal
divisions daughter cells after each
size
round
Total gametes 4 haploid sperm cells 1 haploid ovum plus 2-3 polar
 produced bodies that eventually
in a single cycle degenerate
In humans, the generation of reproductive cells (gametes) occurs in reproductive glands
known as the gonads.  Before puberty, stem cells called spermatogonia undergo continuous
mitotic divisions within the male gonads (ie, testes) to yield identical daughter cells.  At
puberty, spermatogenesis (sperm production) begins and continues throughout the male's
life.

In spermatogenesis, some of the daughter cells produced from mitotic divisions of

spermatogonia become primary spermatocytes.  Primary spermatocytes then become
mature sperm via meiosis, a process involving two rounds of cell division known as
meiosis I and II.  A primary spermatocyte that undergoes meiosis I yields two identical
haploid cells labeled secondary spermatocytes.  Each secondary spermatocyte then
undergoes meiosis II to produce four identical haploid spermatids that develop into mature
sperm.

In contrast to spermatogenesis, oogenesis (oocyte production) begins before birth, not at

puberty, in the female gonads (ie, ovaries) (Choice A).  In the female embryo, oogonia
(stem cells) undergo mitosis to produce primary oocytes.  Each primary oocyte is
surrounded by a saclike structure called a follicle.  Although they must also undergo
meiosis to mature, primary oocytes begin meiosis I but become arrested at prophase I until
puberty.  At puberty, one primary oocyte is selected during each menstrual cycle to
complete meiosis I.

Unlike in spermatogenesis, meiosis I in oogenesis yields two haploid cells of unequal size,
the larger one being a secondary oocyte and the smaller one being a polar body that
eventually degenerates (Choice C).  The secondary oocyte then begins meiosis II but is
arrested at metaphase II.  The secondary oocyte completes meiosis II and fully matures
only if fertilization occurs.  To be fertilized, the secondary oocyte must be released during
the ovulation phase of the menstrual cycle.  During this phase, the follicle ruptures from the
ovary and the oocyte enters the fallopian tube to be fertilized by mature sperm.

(Choice D)  Oogenesis begins before birth but ceases in older women when ovarian
production of female sex hormones declines (ie, menopause).  In contrast, spermatogenesis
begins at puberty and continues throughout the male's life.  Neither process occurs
continuously throughout an organism's entire life-span.

Educational objective:
Both spermatogenesis and oogenesis involve cells that undergo meiosis I and II.  However,
oogenesis in females begins in the female embryo and ends at menopause, whereas
spermatogenesis in males does not begin until puberty and continues throughout a male's
life.