Genetics and inheritance

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Genetics and inheritance
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In your own words, explain the following terms

1. Chromosome
2. Gene
3. Features
4. Gametes
5. Zygote
6. Diploid
7. Allele
8. Homozygous
9. Heterozygous
10. Selective breeding
11. Genetic engineering
12. Meiosis
13. Mitosis
14. Sexual reproduction
15. Asexual reproduction
16. Mutations
17. Dominant
18. Recessive

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chromosome
The instructions that tell cells what we look
like are carried in these. There are 23 pairs of
them in a normal human cell.
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Genes
These are the units which make up chromosomes.
Responsible for inheritance of specific
characteristics
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Cellular Functions of Human Genes
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FEATURES
These are things like eye colour, skin colour
and hair colour. They are controlled by genes.
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gametes
Sperm and egg cells are both this type of
cell. Contain half the amount of DNA of normal
diploid cells
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zygote
When a sperm and egg cell fuse together, they
produce this.
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diploid
We use this word to describe cells which contain
the full complement of genetic material. In
humans this would be 46 chromosomes (23 pairs)
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alleles
The different versions of genes One of two to
many alternative forms of the same gene (eg.,
round allele vs. wrinkled allele yellow vs.
green). Alleles have different DNA sequences that
cause the different appearances we see.
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Homozygous
Alleles of a given gene are identical (can be
either dominant or recessive
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Heterozygous
Alleles of a given gene are not identical
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selective breeding
Where plants and animals with useful or desired
traits are bred together to produce offspring
with those desired traits
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Genetic engineering
The altering of the character of an organism by
inserting genes from another organism
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mitosis
Division of a cell to produce 2 daughter cells
which each has the same number and kind of
chromosomes as the mother cell
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sexual reproduction
Type of reproduction that involves fusion of
gametes
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asexual reproduction
Reproduction whereby individuals are produced
from a single parent
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Mutation
Random change in the genetic material of the cell
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dominant
The allele that is expressed where an individual
is heterozygous
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recessive
The allele that is hidden (not expressed) when
an individual is heterozygous for a given gene
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Mendelian Genetics
The laws of heridity
Gregor Mendel (1822-1884) Father of Genetics
Augustinian Monk at Brno Monastery in Austria
(now Czech Republic)
-gt well trained in math, statistics, probability,
physics, and interested in plants and heredity.
Mountains with short, cool growing season meant
pea (Pisum sativum) was an ideal crop plant.

• Work lost in journals for 50 years!
• Rediscovered in 1900s independently by 3
  scientists
• Recognized as landmark work!

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Garden Pea

• Pisum sativum
• Diploid
• Differed in seed shape, seed color, flower color,
  pod shape, plant height, etc.
• Each phenotype Mendel studied was controlled by a
  single gene.

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Terms

• Wild-type is the phenotype that would normally be
  expected.
• Mutant is the phenotype that deviates from the
  norm, is unexpected but heritable.
• This definition does not imply that all mutants
  are bad in fact, many beneficial mutations have
  been selected by plant breeders.

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Advantages of plants

• Can make controlled hybrids.
• Less costly and time consuming to maintain than
  animals.
• Can store their seed for long periods of time.
• One plant can produce tens to hundreds of progeny.

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Advantages of plants

• Can make inbreds in many plant species without
  severe effects that are typically seen in
  animals.
• Generation time is often much less than for
  animals.
• Fast plants (Brassica sp.)
• Arabidopsis

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Mendelian Genetics
The laws of heridity

• The Law of Segregation
• Genes exist in pairs and alleles segregate from
  each other during gamete formation, into equal
  numbers of gametes. Progeny obtain one
  determinant from each parent.
• -gt Alternative versions of genes account for
  variations in inherited characteristics (alleles)
• -gt For each characteristic, an organism inherits
  two alleles, one from each parent. (-gt
  homozygote/heterozygote)
• -gt If the two alleles differ, then one, the
  allele that encodes the dominant trait, is fully
  expressed in the organism's appearance the
  other, the allele encoding the recessive trait,
  has no noticeable effect on the organism's
  appearance (dominant trait -gt phenotype)
• -gt The two alleles for each characteristic
  segregate during gamete production.

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The Principle of Segregation

• Genes come in pairs and each cell has two copies.
• Each pair of genes can be identical (homozygous)
  or different (heterozygous).
• Each reproductive cell (gamete) contains only one
  copy of the gene.

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Mendels Principle of Segregation

• In the formation of gametes, the paired
  hereditary determinants separate (segregate) in
  such a way that each gamete is equally likely to
  contain either member of the pair.
• One male and one female gamete combine to
  generate a new individual with two copies of the
  gene.

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Principle of Segregation(Mendels First Law)
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Important Observations

• F1 progeny are heterozygous but express only one
  phenotype, the dominant one.
• In the F2 generation plants with both phenotypes
  are observed?some plants have recovered the
  recessive phenotype.
• In the F2 generation there are approximately
  three times as many of one phenotype as the
  other.

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Mendels Results
Parent Cross F1 Phenotype F2 data
Round x wrinkled Round 5474 1850
Yellow x green Yellow 6022 2001
Purple x white Purple 705 224
Inflated x constricted pod Inflated 882 299
Green x yellow pod Green 428 152
Axial x terminal flower Axial 651 207
Long x short stem Long 787 277
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3 1 Ratio

• The 3 1 ratio is the key to interpreting
  Mendels data and the foundation for the the
  principle of segregation.

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Round vs. Wrinkled
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A Molecular View
Parents
F1
F2 Progeny
WW ww Ww ¼WW ¼Ww ¼wW ¼ww
1 2 1 Genotype 3 1 Phenotype
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One Example of Mendels Work
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Dihybrid crosses reveal Mendels law of
independent assortment

• A dihybrid is an individual that is heterozygous
  at two genes
• Mendel designed experiments to determine if two
  genes segregate independently of one another in
  dihybrids
• First constructed true-breeding lines for both
  traits, crossed them to produce dihybrid
  offspring, and examined the F2 for parental or
  recombinant types (new combinations not present
  in the parents).

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Mendel and two genes
Round Yellow
Wrinkled Green
x
All F1 Round, Yellow
Wrinkled Yellow 101
Wrinkled Green 32
Round Yellow 315
Round Green 108
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Dihybrid cross produces a predictable ratio of
phenotypes

• genotype phenotype number
  phenotypic ratio
• Parent Y_R_ 315 9/16
• Recombinant yyR_ 108 3/16
• Recombinant Y_rr 101
  3/16
• Parent yyrr 32 1/16
• Ratio of yellow (dominant) to green
  (recessive)31 (124)
• Ratio of round (dominant) to wrinkled
  (recessive)31 (124)

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Ratio for a cross with 2 genes

• Crosses with two genes are called dihybrid.
• Dihybrid crosses have genetic ratios of 9331.

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Mendel and two genes
Wrinkled Yellow 101
Wrinkled Green 32
Round Yellow 315
Round Green 108
Yellow 416 Green 140
Round 423 Wrinkled 133
Each gene has a 3 1 ratio.
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Summary of Mendel's work

• Inheritance is particulate - not blending
• There are two copies of each trait in a germ cell
• Gametes contain one copy of the trait
• Alleles (different forms of the trait) segregate
  randomly
• Alleles are dominant or recessive - thus the
  difference between genotype and phenotype
• Different traits assort independently

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Rules of Probability
Independent events - probability of two events
occurring together What is the probability that
both A and B will occur? Solution determine
probability of each and multiply them
together. Mutually exclusive events -
probability of one or another event occurring.
What is the probability of A or B
occurring? Solution determine the probability
of each and add them together.
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Mendelian Genetics
The laws of heridity
2. The Law of Independent Assortment Members of
one pair of genes (alleles) segregate
independently of members of other pairs. -gt The
emergence of one trait will not affect the
emergence of another. -gt mixing one trait always
resulted in a 31 ratio between dominant
and recessive phenotypes -gt mixing two
traits (dihybrid cross) showed 9331
ratios -gt only true for genes that are not linked
to each other
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9331
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Linked Genes

• Genes found on same chromosome will be inherited
  together
• do not exhibit independent assortment

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Problems with doing human genetics-gt Cant
make controlled crosses!-gt Long generation
time-gt Small number of offspring per crossSo,
human genetics uses different methods!!
Mendelian Genetics
The laws of heridity
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Major method used in human genetics is -gt
pedigree analysis(method for determining the
pattern of inheritance of any trait)Pedigree
s give information on-gt Dominance or
recessiveness of alleles-gt Risks
(probabilities) of having affected offspring
Mendelian Genetics
The laws of heridity
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Standard symbols used in pedigrees
Mendelian Genetics
The laws of heridity
carrier
inbreeding
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Most dominant traits of clinical significance are
rareSo, most matings that produce affected
individuals are of the formAa x aa
Modes of Heredity
Autosomal Dominant
-gt Affected person can be heterozygote (Aa) or
homozygote (AA) -gt Every affected person must
have at least 1 affected parent -gt expected that
50 are affected /50 are uneffected -gt No
skipping of generations -gt Both males and
females are affected and capable of transmitting
the trait -gt No alternation of sexes we see
father to son, father to daughter, mother to son,
and mother to daughter
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Autosomal dominant disorders

• both homozygotes and heterozygotes are affected
• usually heterozygotes (inherited from one parent)
• both males and females are affected
• transmission from one generation to the other
• 50 of children are affected

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Modes of Heredity
Autosomal Dominant
Examples Tuberous sclerosis (tumor-like
growth in multiple organs, clinical
manifestations include epilepsy, learning
difficulties, behavioral problems, and skin
lesions) and many other cancer causing
mutations such as retinoblastoma Brachydactyly

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Modes of Heredity
Autosomal Dominant
Examples Achondroplasia -gt short limbs, a
normal-sized head and body, normal intelligence
-gt Caused by mutation (Gly380Arg mutation in
transmembrane domain) in the FGFR3 gene -gt
Fibroblast growth factor receptor 3 (Inhibits
endochondral bone growth by inhibiting
chondrocyte proliferation and differentiation
Mutation causes the receptor to signal even in
absence of ligand -gt inhibiting bone growth
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These are likely to be more deleterious than
dominant disorders, and so are usually very rare
The usual mating
is Aa x Aa
Modes of Heredity
Autosomal Recessive
-gt Affected person must be homozygote (aa) for
disease allele -gt Both parents are normal, but
may see multiple affected individuals in the
sibship, even though the disease is very rare in
the population -gt Usually see skipped
generations. Because most matings are with
homozygous normal individuals and no offspring
are affected -gt inbreeding increases
probablility that offspring are affected -gt
unlikely that affected homozygotes will live to
reproduce
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Autosomal recessive

• majority of mendelian disorders
• only homozygotes are affected, heterozygotes
  (parents) are only carriers
• 25 of descendants are affected
• if the mutant gene occurs with low frequency -
  high probability in consanguineous marriages
• onset of symptoms often in childhood
• frequently enzymatic defect
• testing of parents and amnial cells

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Modes of Heredity
Autosomal Recessive
Examples Sickle-Cell Anaemia (sickling occurs
because of a mutation in the hemoglobin gene -gt
affects O2 transport occurs more commonly in
people (or their descendants) from parts of
tropical and sub-tropical regions where malaria
is common -gt people with only one of the two
alleles of the sickle-cell disease are more
resistant to malaria) Cystic fibrosis (also
known as CF, mucovoidosis, or mucoviscidosis
disease of the secretory glands, including the
glands that make mucus and sweat excess mucus
production -gt causing multiple chest infections
and coughing/shortness of breath especially
Pseudomonas infections are difficult to treat -gt
resistance to antibiotica)
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Modes of Heredity
Dominant vs. Recessive
Is it a dominant pedigree or a recessive
pedigree? 1. If two affected people have an
unaffected child, it must be a dominant pedigree
A is the dominant mutant allele and a is the
recessive wild type allele. Both parents are Aa
and the normal child is aa. 2. If two unaffected
people have an affected child, it is a recessive
pedigree A is the dominant wild type allele and
a is the recessive mutant allele. Both parents
are Aa and the affected child is aa. 3. If every
affected person has an affected parent it is a
dominant pedigree.
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Modes of Heredity
X-Linked Recessive
-gt Act as recessive traits in females (XX) -gt
females express it only if they get a copy from
both parents) -gt dominant traits in males
(XY) -gt An affected male cannot pass the trait
on to his sons, but passes the allele on to all
his daughters, who are unaffected carriers -gt A
carrier female passes the trait on to 50 of her
sons Examples About 70 pathological traits
known in humans -gt Hemophilia A, Duchenne
muscular dystrophy, color blindness,..
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X-linked diseases

• transmitted by heterozygous mother to sons
• daughters - 50 carriers, 50 healthy
• sons - 50 diseased, 50 healthy
• Children of diseased father - sons are healthy,
  all daughters are carriers
• Hemophilia A
• Hemophilia B
• Muscle dystrophy
• -gtMost of mental retardation

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Modes of Heredity
Other sex-linked disease
X-linked dominant -gt caused by mutations in
genes on the X chromosome -gt very rare cases -gt
Males and females are both affected in these
disorders, with males typically being more
severely affected than females. -gt Some X-linked
dominant conditions such as Rett syndrome,
Incontinentia Pigmenti type 2 and Aicardi
Syndrome are usually fatal in males Y-linked
(dominant) -gt mutations on the Y chromosome.
-gt very rare cases -gt Y chromosme is small -gt
Because males inherit a Y chromosome from their
fathers -gt every son of an affected father will
be affected. -gt Because females inherit an X
chromosome from their fathers -gt female offspring
of affected fathers are never affected. -gt
diseases often include symptoms like infertility
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Modes of Heredity
Exceptions to Mendelian Inheritance
Mitochondrial inheridance Mitochondrial DNA is
inherited only through the egg, sperm
mitochondria never contribute to the zygote
population of mitochondria. There are relatively
few human genetic diseases caused by
mitochondrial mutations. -gt All the
children of an affected female but none of the
children of an affected male will inherit the
disease. -gt Note that only 1 allele is present in
each individual, so dominance is not an issue
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Summary of mutations which can cause a disease

• Three principal types of mutation
• Single-base changes
• Deletions/Insertions
• Unstable repeat units
• Two main effects
• Loss of function
• Gain of function

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Pedigree

• Use Mendelian principles to assemble information
  on family traits
• Study inheritance patterns when cant perform
  test cross
• Genetic counseling
• Track genetic disorders
• Carriers
• Carry allele for recessive disorder- do not
  exhibit symptoms

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Albinism Pedigree
Carrier
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Single gene disorders

• One gene controls the disorder
• Exhibit simple inheritance patterns
• Can be dominant or recessive

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Recessive Disorder

• Homozygous recessive
• Bulk of human genetic disorders
• Vary in effect
• Albinism
• Tay Sachs
• Inbreeding
• Mating of close relatives
• Increases frequency of homozygous recessive
  genotypes??

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Albinism
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Inbreeding
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Polydactyly
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Dominant Disorders

• Disease expressed with only 1 allele present
• Maintained in population because
• Not lethal
• Achondroplasia
• Webbing
• Extra digits
• Develop post- reproductive age
• Huntington disease

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Dominant disordersSyndactyly
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Dominant disorders Polydactyly
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Achondroplasia
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Other Patterns of Inheritance

• Incomplete dominance
• Codominance
• Pleiotrophy
• Polygenic inheritance

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Incomplete dominance

• Pattern of inheritance in which the heterozygous
  (Aa) phenotype is intermediate between the
  phenotypes of the homozygous parents (AA aa)

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Incomplete Dominance
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Sickle Cell ANemia
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codominance

• The expression of two different alleles of a gene
  in a heterozygous condition
• Example AB0 blood group

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Co dominance
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Pleiotropy

• The control of more than one phenotypic
  characteristic by a single gene
• One gene many effects

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Polygenic inheritance

• The additive effect of two or more gene loci on a
  single phenotypic characteristic
• Majority of characteristics
• Example skin color

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Polygenic inheritance
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Sex-chromosomes
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Sex linked genes

• Gene located on a sex chromosome
• X chromosome contains more genes than Y
  chromosome
• Sex linked inheritance
• Males pass y linked only to sons
• Males pass x linked only to daughters
• Females can pass x linked to either sons or
  daughters

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Sex linked disorders

• Recessive sex linked
• Y linked recessive always exhibited in males
• X linked recessive exhibited in males and
  homozygous females
• X linked dominant traits exhibited in both Males
  female carriers
• Color blindness (X)
• Hemophilia
• X linked recessive

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Hemophilia
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Y Linked disorders

• Androgen Insensitivity disorder
• XY genetics yield female phenotype as a result of
  an inability to respond to testosterone
• Error in membrane protein receptors
• Congenital adrenal hyperplasia
• Xx genotype yield female with male genitalia
• Masculinization of genitals defects in adrenal
  gland function

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Translocation

• Deletion
• Loss
• Duplication
• Added chromosome

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Fragile X Syndrome
Duplication