Download Basic Genetics Concepts

Basic Genetics Concepts
The Basics
• Genes are the units of heredity: they determine all aspects of our bodies and
how they work.
• Note: we are talking about genes as abstract entities here, not about the physical details of
DNA sequences.
• We are the product of our genes, but there are many event and interactions
between our genes and our physical bodies. That is, the phenotype of an
individual is not always obvious from the genotype.
• Genotype: our genetic constitution. Ultimately, this means our DNA sequence.
• Phenotype: our physical appearance and condition.
• We humans are diploid: we have 2 copies of every gene, one copy from the
mother and one copy from the father.
• Diploidy implies that every trait is determined (or “conditioned”) by 2 copies of a
gene, which might not be identical.
• Alleles: different versions of a gene (as we now know, different alleles have slightly different
DNA sequences)
• Homozygous: both copies of a gene are identical: same allele
• Heterozygous: the two copies of a gene are different: different alleles.
Dominance
• Dominance is a description of how 2 different alleles
interact, the phenotype associated with different
possible genotypes at a single gene.
• For convenience in these examples, we will call one allele A and
the other allele a.
• Complete dominance: the phenotype of the
heterozygote is the same as one of the homozygotes: AA
and Aa have the same phenotype, which is different
from aa. This is the type of dominance seen by Mendel.
• In this example, A is the dominant allele (whose phenotype is
seen in the heterozygote) and a is the recessive allele
(phenotype seen in aa homozygotes but not in the
heterozygote).
• Many human genetic diseases are recessive: only the
homozygotes show a mutant phenotype, while the
heterozygotes appear normal. That is, the normal allele is
completely dominant to the disease allele.
• The heterozygotes for recessive disease are called carriers.
More Dominance
• Partial dominance (sometimes called incomplete
dominance): when the heterozygote has a
phenotype different from either homozygote:
AA, Aa, and aa all have distinctly different
phenotypes.
• Often the heterozygote’s phenotype is intermediate
between the two homozygotes.
• A common example: an AA plant has red flowers, and
aa plant has white flowers, and an Aa plant has pink
flowers (intermediate between red and white).
• Most dominant genetic disease in humans are actually
partially dominant: the heterozygote has a mutant
phenotype, while the dominant homozygote either
dies before birth or is extremely defective with very
low chances of survival.
More Dominance
• Co-dominance: when the heterozygote
shows the phenotypes of both parents.
• Co-dominance is mostly seen at the level
of molecular markers: if you are a
heterozygote for a given gene, DNA
sequencing will detect the 2 different
sequences.
• Also often seen with proteins that have
slightly different properties such as
mobility on an electrophoresis gel, or
different blood types.
Penetrance as a Confounding Variable
• Penetrance: the percentage of individuals with a
mutant genotype that express the mutant
phenotype.
• The expression of many genes is affected by various
environmental conditions and by other genes in the
genome.
• Often, individuals who have a genotype that should
give them a mutant phenotype appear normal instead.
A gene that displays this phenomenon is said to have
incomplete penetrance.
• Incomplete penetrance is very common in humans,
which causes a lot of difficulties in determining
dominance and inheritance patterns. Offspring ratios
are not what they should be, for instance.
• Closely related: variable expressivity = the degree of
expression of the mutant gene is variable.
The Sexual Cycle
• We reproduce sexually: every individual has two
different parents.
• Cloning means having only 1 parent, with the offspring
genetically identical to the parent.
• Cloning is common in plants and some lower animals,
and can be done artificially in some mammals. However,
it is not currently possible in humans.
• We are diploid, but to reproduce we need haploid
gametes.
• Gametes: sperm or eggs
• Haploid: 1 copy of each gene
• The sexual cycle of humans (and most other
eukaryotes):
• A diploid cell is reduced to haploid by the cell division
process of meiosis.
• Two haploid cells combine to form a new diploid cell by
the process of fertilization. The first diploid cell of the
next generation, the fertilized egg, is called a zygote.
Segregation of Genes into Gametes
• The two copies of each gene go randomly and
equally into the gametes, which then combine at
random to form the next generation.
• Each gamete gets one copy of each gene, chosen
randomly. As a consequence, both copies of the gene
have an equal chance of ending up in a gamete.
• Mendel’s Law of Segregation
• A consequence of meiosis.
• Leads to simple, easily recognized inheritance
patterns
• Two heterozygotes (normal carriers) of a recessive trait
produce 1/4 mutant offspring and 3/4 normal.
• A heterozygote for a dominant trait mating with a
homozygous normal person produces 1/2 affected
offspring and 1/2 normal offspring.
• Some variants:
• Two heterozygotes for a dominant trait should produce
3/4 affected offspring, but if the dominant
homozygous condition is lethal, the ratio is reduced to
2/3.
• A heterozygote for a recessive trait mating with a
homozygous normal individual produce all normal
offspring. This is a way to avoid producing children
with mutant phenotypes.
Independent Assortment and Linkage
• Within a species, genes are found in fixed positions: at
the same chromosomal location in all individuals.
• Even between closely related species, most genes are in the
same relative positions.
• When looking at 2 different genes, their alleles go into
gametes independently of each other (usually). That
is, they assort independently.
• Mendel’s Law of Independent Assortment, which generates
the classic 9:3:3:1 ratios in crosses involving 2 genes.
• However, genes that are close together on the same
chromosome tend to go into gametes together: genes
that do not assort independently are linked.
• How frequently 2 genes stay together is a function of how far
apart they are on the chromosome: the closer they are, the
more tightly they are linked.
• Mendel did not observe linkage: he didn’t look at enough
genes.
• Linkage is the basis for gene mapping
Recombination
• The two copies of each chromosome (one from each
parent) are called homologues.
• During prophase of the first meiotic division, the
homologues pair up, and at several random locations
on every chromosome, they break and rejoin, so each
chromosome after this is a mixture of segments from
the two parents. This is the process of recombination,
also called crossing-over.
• Linkage can be seen when 2 genes close together are both
heterozygous: for example when the alleles on one
chromosome are A and B, and the alleles on the other
chromosome are a and b. That is: A B / a b
• If a crossover event occurs between these two genes, the
resulting chromosomes will be A b and a B. These are
called recombinant chromosomes.
• If no crossover occurred between the 2 genes, the
resulting chromosomes will be A B and a b. These are
called parental chromosomes, because the alleles are in
the same configuration as in the original parents.
More Recombination
• The closer 2 genes are to each other, the more likely it is they
there will not be a recombination event between them. That is,
the offspring will have more A B and a b parental chromosomes
than A b and a B recombinant chromosomes. In this case, genes
A and B are said to be linked.
• However, when 2 genes are far enough apart, there can be
multiple crossovers between them. Since you can’t detect these
events directly, 2, 4, or 6 crossovers give the same result as 0
crossovers (parental configuration), and any odd number of
crossovers between 2 genes looks like a single crossover
(recombinant configuration).
• Two consequences of this:
1. The maximum percentage of recombinant offspring is 50%. The
frequency of A B and a b parental chromosomes in the offspring
is the same as the frequency of A b and a B recombinant
chromosomes. In this cases, genes A and B are unlinked.
2. Genes far enough apart on the same chromosome appear to be
unlinked.
Gene Mapping
• When mapping an organism like Drosophila, one usually
examines flies containing several different mutant genes.
However, it is rare for any human to have 2 mutant genes that
give clear visible phenotypes.
• Rather than map genes relative to each other, genes are usually
mapped relative to various genetic markers. Genetic markers are
loci (sites at specific locations; singular of loci is locus) on the
chromosome that have a different sequence in different
individuals.
• Most common markers today are single nucleotide polymorphisms
(SNPs), where many people will have one nucleotide, say a G, while
many others have another nucleotide, say an A.
• Genetic markers are inherited between generations, and they can be
detected and used for maps just like visible mutant phenotypes.
• Most genetic markers have no obvious effect on the person’s phenotype.
• There are several million different SNP markers known, so there are
always several near any gene.
• Using genetic markers it is possible to build up a map of all the
chromosomes, knowing where all the markers are relative to each
other , to the genes, and to the known DNA sequence of the
chromosomes.
• Compared to Drosophila, humans have very few offspring, and
they don’t mate in a controlled fashion. Special techniques are
needed to map human genes, combining the information from
many crosses together.
Genes on the X and Y Chromosomes
• The X and Y chromosomes determine sex in humans: the
usual condition is that males have an X and a Y (XY) and
females have 2 X chromosomes (XX).
• The X chromosome has many genes on it, most of which
have nothing to do with sex.
• There are only a few genes on the Y chromosome
• Genes on the X chromosome are called sex-linked,
because their inheritance goes along with the inheritance
of sex.
• Since males have only 1 X chromosome, any mutations on
that chromosome are expressed, whether dominant or
recessive.
• The effect is that most sex-linked mutations are seen in 10
times (or more) as many males as females.
• Genes present in only 1 copy, such as genes on the X in males,
are called hemizygous.
• Sex-linked genes have a unique pattern of inheritance.
• Because of this, the first human genes to be mapped to a
chromosome were all sex-linked.
Chromosomes
• Key features of a chromosome: centromere (where spindle attaches), telomeres (special structures at
the ends), arms (the bulk of the DNA).
• Chromosomes come in 2 forms, depending on the stage of the cell cycle. The monad form consists of a
single chromatid, a single piece of DNA containing a centromere and telomeres at the ends. The dyad
form consists of 2 identical chromatids (sister chromatids) attached together at the centromere.
• Chromosomes are in the dyad form before mitosis, and in the monad form after mitosis.
• The dyad form is the result of DNA replication: a single piece of DNA (the monad chromosome)
replicated to form 2 identical DNA molecules (the 2 chromatids of the dyad chromosome).
• Diploid organisms have 2 copies of each chromosome, one from each parent. The two members of a
pair of chromosomes are called homologues.
• Each species has a characteristic number of chromosomes, its haploid number n. Humans have n=23,
that is, we have 23 pairs of chromosomes. Drosophila have n=4, 4 pairs of chromosomes.
Cell Cycle
• The cell cycle is a theoretical concept that defines the state of the cell
relative to cell division.
• The 4 stages are: G1, S, G2, and M.
• M = mitosis, where the cell divides into 2 daughter cells. The
chromosomes go from the dyad (2 chromatid) form to the monad (1
chromatid) form. That is, before mitosis there is 1 cell with dyad
chromosomes, and after mitosis there are 2 cells with monad
chromosomes in each.
• S = DNA synthesis. Chromosomes go from monad to dyad.
• G1 = “gap”. Nothing visible in the microscope, but this is where the
cell spends most of its time, performing its tasks as a cell. Monad
chromosomes.
• Cells not actively dividing are said to be in the G0 state, which is just like G1 with
monad chromosomes
• G2 (also “gap”). Dyad chromosomes, cell getting ready for mitosis.
• G1, S, and G2 are collectively called “interphase”, the time between
mitoses
Mitosis
• Mitosis is ordinary cell division among the cells of the body. During
mitosis the chromosomes are divided evenly, so that each of the two
daughter cells ends up with 1 copy of each chromosome.
• For humans: start with 46 dyad chromosomes in 1 cell, end with 46
monads in each of 2 cells.
• Stages: prophase, metaphase, anaphase, telophase.
Stages of Mitosis
• Prophase:
--chromosomes condense
--nuclear envelope disappears
--centrioles move to opposite ends of the cell
--spindle forms
• Metaphase:
--chromosomes are lined up on cell equator, attached to the spindle at the
centromeres
• Anaphase:
--centromeres divide. Now chromosomes are monads
--the monad chromosomes are pulled to opposite poles by the spindle.
• Telophase:
--cytokinesis: cytoplasm divided into 2 separate cells
--chromosomes de-condense
--nuclear envelope re-forms
--spindle vanishes
Meiosis
• Meiosis is the special cell division that converts diploid body cells into
the haploid gametes. Only occurs in specialized cells.
• Takes 2 cell divisions, M1 and M2, with no DNA synthesis between.
• In humans, start with 46 chromosomes (23 pairs) in dyad state.
• After M1, there are 2 cells with 23 dyad chromosomes each.
• After M2 there are 4 cells with 23 monad chromosomes each.
First Meiotic Division (M1)
• Prophase of M1 is very long, with a number of sub-stages.
• Main event in prophase of M1 is crossing over, also called
recombination.
• In crossing over, homologous chromosomes pair up (this pairing is
called synapsis), and exchange segments by breaking and rejoining at
identical locations.
• Several crossovers per chromosome, with random positions. This is
the basis for linkage mapping.
• In metaphase of M1, pairs of homologous chromosomes line
up together.
• In mitosis and M2, chromosomes line up as single individuals.
• Anaphase of M1: the spindle pulls the two homologues to
opposite poles. However, the centromeres don’t divide, and
the chromosomes remain dyads.
• Telophase of M1: cytoplasm divided into 2 cells, each of which
has 1 haploid set of dyad chromosomes
Second Meiotic Division (M2)
• Meiosis 2 is just like mitosis.
• In prophase, the chromosomes condense and the spindle forms.
• Metaphase of M2: dyad chromosomes line up singly on the cell equator.
• Anaphase of M2: centromeres divide, chromosomes are now monads
which get pulled to opposite poles.
• Telophase: cytoplasm divided into 2 cells.
• After M2: total of 4 cells from the original cell. Each contains one
haploid set of monad chromosomes
Gene Balance and Chromosome Rearrangement
• For many genes, it is necessary to have exactly 2
functional copies present. Having 1 copy or 3 copies
leads to abnormalities.
• The amount of gene product needs to be carefully
balanced against products form other genes
• Not all genes need this
• Having equal numbers of every gene and every
chromosome is called euploid. Not having equal
numbers of all genes and chromosomes is aneuploid.
• There are some special rules for genes on the X
chromosome
• Two main ways to become aneuploid:
• Gain or lose a whole chromosome through non-disjunction
in meiosis
• Chromosome structural changes
Non-disjunction
• In meiosis 1, the homologous chromosomes are
paired. Normally, one member of the pair goes
to each of the spindle poles when the
chromosomes separate in anaphase 1.
• In meiosis 2, the dyad chromosomes split into 2
monad chromosomes in anaphase. One monad
of each pair of monads migrates to each of the
spindle poles.
• In non-disjunction, both members of a pair
migrate to the same pole.
• Happens spontaneously
• Can occur in meiosis 1 or meiosis 2
• Results in aneuploid gametes: a gamete with either 0
or 2 copies of a chromosome instead of 1.
Chromosome Structural Changes
• Chromosomes are long and fragile, and sometimes they break. The cell has
mechanisms to re-attach broken ends, but sometimes the wrong ends get
attached together. This results in structural changes: inversions, deletions,
duplications, and translocations.
•
•
•
•
Inversion: a piece of chromosome is inserted backwards
Deletion: a piece of chromosome is missing
Duplication: a piece of chromosome is present in 2 copies
Translocation: a piece of chromosome has been moved to a different
chromosome
• Between species, chromosomal rearrangements are common, and they
often prevent the production of viable hybrid offspring.
More Structural Changes
• Most chromosome structural changes involve
several or many genes. Some genes can tolerate
aneuploidy, while others are very sensitive to it.
• The chromosome breaks themselves can cause
genetic harm, if they break a gene in half.
Otherwise, any genetic harm is due to aneuploidy.
• Most of the time, a person is heterozygous for the
unusual chromosomes: they also have a set of
normal chromosomes .
• Organisms that are heterozygous for deletions and
duplications are aneuploid: they have 1 copy or 3
copies of the genes involved.
• Inversions and translocations are often euploid
initially, but the offspring end up aneuploid due to
crossing over and chromosome segregation in
meiosis.
Some Population Genetics Concepts
• A population is a group of individuals from the same species
who interbreed freely.
• There is only 1 human population, but some species have several
non-overlapping habitats, creating different populations.
• Many genes are polymorphic: at least 2 alleles present in the
population.
• In human genetics, 2 or more alleles have to be present in at least
1% of individuals.
• The ABO blood group is a polymorphic genes: 3 alleles are all
present in the human population at reasonably high frequencies.
• Allele frequency and genotype frequency. For a gene with 2
alleles, A and a, there are 3 possible genotypes: AA, Aa, and aa.
• Genotype frequency = the number of individuals with a given genotype
divided by the total number of individuals in the population. Genotype
frequency is directly observed.
• Allele frequency = number of genes with a given allele divided by the total
number of genes in the population. Since we are diploid, the allele
frequency is derived from the genotype frequencies. The frequency of
allele A equals the frequency of AA individuals plus half the frequency of Aa
heterozygotes.
Hardy-Weinberg Equilibrium
• If a gene is not being acted upon by any evolutionary forces,
the allele frequencies are related to the genotype
frequencies by a simple equation.
• These frequencies are stable from generation to generation.
• If the genotype frequencies predicted from the allele
frequencies don’t match the actual genotype frequencies,
the population is evolving, by violating one or more of the 5
conditions necessary for Hardy-Weinberg equilibrium:
1.
2.
3.
4.
5.
No mutations
No migration in or out of the population
Random mating
Very large population
No selection favoring one genotype over another
Selection
• The most interesting of the H-W conditions is “no
selection”. Darwin’s theory of evolution by natural
selection says that most major changes come from
natural selection in favor of one trait compared to
other traits.
• In population genetics terms, this means one
genotype has a higher fitness (ability to survive and
reproduce) than other genotypes
• Common selection patterns:
• Selection against a recessive homozygote. The
frequency of the less fit allele decreases every
generation
• Selection in favor of the heterozygote. Both alleles
are maintained in the population. A good example is
sickle cell anemia, where the AS heterozygous
genotype is the most fit genotype in places where
malaria is prevalent. A = normal beta globin and S =
sickle cell beta-globin (which causes malaria
resistance).
Genetic Drift
• Also important for H-W equilibrium is population size. In small isolated
populations, allele frequencies can change very rapidly due to random
events: who mates with who, fatal accidents, …
• Genetic drift: random changes in allele frequencies within a population.
• Genetic drift has its largest effects on small populations.
• If a population goes through a bottleneck (gets reduced to a very small
number), only those alleles present among the survivors get into future
generations.
• This can also be called the founder effect: only the alleles present in the
founders of a new population occur in future generations.
• Can lead to otherwise rare alleles being common in small isolated populations
• Genetic drift can lead to fixation of an allele: all members of the
population are homozygous for that allele, and there are no other alleles
present.
• Neutral mutations are alleles that are not affected by natural selection:
they are selectively neutral. However, genetic drift can cause neutral
mutations to decrease or increase their frequency, and even become fixed
in the population.
• Both selection and drift are important forces in evolution. Which force is
more important depends on the circumstances.
Quantitative Genetics
• Many traits are clearly inherited, but show continuous variation rather
than having 2 distinctly different alleles: height, skin color, intelligence for
example.
• Traits that show continuous variation are called quantitative traits.
• Quantitative traits usually show a normal distribution (also called a Gaussian
distribution or a bell shaped curve)
• The phenotype of quantitative traits is affected by both genetics and the
environment: the bottom line of quantitative genetics
• Mathematically, the total phenotypic variance is the sum of the variance due
to genetics plus the variance due to the environment
• VT = VG + VE
• The proportion of the variance due to genetics is called the heritability
• H = VG / VT
• Often the genetic part is polygenic: many genes involved, each
contributing a small part of the phenotype
• Sometime oligogenic: a few genes involved, each contributing to the
phenotype.
Principles of Development
• How to get from a single cell, the zygote, to a multicellular organism.
• General events:
• cell division and growth
• differentiation: cells develop different phenotypes
• pattern formation: overall development of body axes, the general body plan,
and structure of individual organs
• morphogenesis: changes in shape
Canalization of Development
• Cells become increasingly specialized during development. Their
range of possible fates (final cell type) decreases. This is called the
canalization of development.
• Initially, cells of the embryo are totipotent: can develop into any
embryonic cell. After a while, embryo is divided into a trophoblast
and an inner cell mass. Inner cell mass become the embryo while
trophoblast becomes outer membranes and placenta. Cells in ICM
can become any embryonic tissue, but they can’t become
trophoblast cells: these cells are pluripotent. As development
proceeds, embryonic cells become increasingly specialized and can
no longer become any final cell type: they become multipotent and
finally unipotent when they can only become one final cell type.
• At some point, a cell is determined to be a particular cell type.
Determination is followed by differentiation, changes of form and
function, into that cell type.
• decisions about determination are caused by a cell’s lineage:
previous decisions, by its position in the embryo, and by signals
passed between the cells.
Stem Cells
• Stem cells are self-renewing cells that differentiate into a variety of
cell types. After a stem cell divides, one daughter cell typically
remains a stem cell, while the other one starts to differentiate into
a final cell type: this is called asymmetric cell division.
• There are many types of stem cell in adults, and they are generally
rare and hard to find. Some differentiate into a single cell type,
while others can have multiple fates.
• Embryonic stem cells are the pluripotent cells of the inner cell
mass, which can become any kind of embryonic cell.
Pattern Formation
• How does the basic body plan get formed
• axes: dorsal-ventral (back-front), cranial-caudal (head-tail), left-right.
• position within an organ: e.g. how to get 5 different fingers on a hand
• axis development: based partly an uneven distribution of
components in the egg and partly on external events.
• sperm entry point determines boundary between trophoblast and
inner cell mass, which in turn determines the dorsal-ventral axis
• cranial-caudal axis probably determined by position of second polar
body exit relative to sperm entry point
• morphogen gradients. Certain cells secrete chemicals that act as
morphogens: signals that allow other cells in that tissue to
determine their position in the tissue. The farther a cell is from the
morphogen secretion site, the lower the concentration of the
morphogen.
• a well known example is the zone of polarizing activity, which occurs in
limb buds. Cells nearest the ZPA become the little finger or toe, while
those farthest away become the thumb or big toe.
Hox genes
• Animal development along an axis,
from Drosophila to humans, is
largely determined by clusters of
homeobox (Hox) genes.
• Different members of the Hox
clusters are activated in different
parts of the morphogen gradient,
in an overlapping pattern
• The Hox gene products then
stimulate the activity of other
genes that cause the cells to
differentiate into the proper type.
Fertilization
• Egg is surrounded by two layers of extracellular
matrix, the vitelline membrane and the zona
pellucida. The sperm cells must dissolve their way
through these layers to get to the egg. Sperm
contain an acrosome at their tips that contains the
necessary enzymes.
• When a sperm reaches the egg membrane, the
membranes fuse, putting the sperm nucleus inside
the egg.
• Egg membrane then depolarizes and cortical
granules release their contests to push all other
sperm cells away.
• Meiosis 2 occurs and the second polar body exits
opposite the sperm entry point.
• the male and female pronuclei then undergo
mitosis together, and the resulting nuclei fuse.
• Fertilization occurs in the Fallopian tubes. After
fertilization, the embryo takes about a week to
reach the uterus.
Early Development
• The early cell divisions of the embryo occur without any overall growth. These divisions, the
cleavage divisions, result in the morula, a ball of 16 or more cells. Each cell is called a blastomere.
• After a few more divisions, cells on the outside of the morula flatten out, and the inside develops
into a hollow ball, the blastocyst.
• On one side of the blastocyst a clump of cells, the inner cell mass, forms. The inner cell mass
develops into the embryo and the amnion, the inner membrane.
• The other cells of the blastocyst are called the trophoblast (trophoectoderm), The trophoblast
forms the chorion, the outer membrane of the embryo, and the embryonic part of the placenta
(which is also composed of maternal tissues).
• At about 5 days after fertilization, the blastocyst hatches by releasing itself from the zona pellucida
that surrounded the egg, Then implantation into the uterine wall occurs, about 6 days postfertilization.
Gastrulation
• Lewis Wolpert: “It is not birth, marriage, or death, but
gastrulation, which is truly the important event in your
life.”
• About 3 weeks after fertilization, the cells of the inner cell
mass undergo a series of movements that end up
producing the three fundamental germ layers of the body:
ectoderm, mesoderm, and endoderm. Also, body
orientation gets established.
• ectoderm turns into skin and nervous system
• mesoderm turns into muscle, bone, circulatory system,
kidneys
• endoderm turns into gut lining, endocrine glands, most
internal organs
• Cells in one area of inner cell mass develop a primitive
streak, an area where the cells start to move inward. The
cells that end up inside become the endoderm, while the
cells that remain outside become the ectoderm. The
mesoderm develops last, from cells near the primitive
streak.
• The primitive streak is replaced by the notochord, a rod of
cartilage that is the defining characteristic of the
chordates (which includes the vertebrates).
Neurulation
• After gastrulation finishes, about 4 weeks after
fertilization, the nervous system starts to form,
• The first event is the induction of the neural
tube (beginning of the spinal cord) by the
notochord interacting with the ectoderm above
it. If the tube fails to close, spina bifida or
anencephaly (absence of a brain) results.
• Induction is a developmental process in which cells of one
type touch cells of another type and induce them to
differentiate into a new pattern.
• Neural crest cells form at the margins of the
neural tube. These cells migrate laterally,
forming the peripheral nervous system,
melanocytes (pigment cells).
• This period ends after about 8 weeks, after
which the embryo is called a fetus, which grows
and develops further.
Twinning
• 2 basic types: dizygotic (fraternal): develop from 2
separate eggs fertilized by separate sperm. Nothing
more than siblings who happen to share a womb.
• monozygotic (identical): develop from one fertilized egg,
with the embryo splitting into 2 early in development.
Cause is unknown.
• Cells up to the 4 cell stage are pluripotent: any single
cell can develop into a whole person. This limits
identical siblings to quadruplets.
• splitting the embryo after about 12 days of development
can be incomplete, resulting in conjoined twins. The
joined region can include almost any area of the body
and any degree of completeness.
• A split before 4 days gives separate placentas
• 4-8 day gives a shared placenta but separate amniotic sacs
• 8-12 day split gives shared amniotic sacs, but still two
separate individuals
• 13-15 day splits are usually incomplete, resulting in
conjoined twins.
• A competing theory says that you start with a fertilized
egg, the embryo splits completely, and then stem cells
seeking similar cells cause them to re-fuse.