ABNORMAL

CHROMOSOME NUMBER
DANIEL H. BERCEDE, RMT
When Gene Expression Appears to Alter
Mendelian Ratios
 Account for atleast 50% of spontaneous abortions, yet
only 0.65% of newborns have abnormal chromosomes.

 Therefore,
most embryos and fetuses with abnormal
chromosome stop developing before birth
Non-disjunction
 thefailure of homologous chromosomes or sister
chromatids to separate properly during cell division.
 Types of chromosome abnormalities
Type of Abnormality Definition
Polyploidy Extra chromosome sets
Aneuploidy An extra or missing chromosome
Monosomy One chromosome absent
Trisomy One chromosome extra
Deletion Part of a chromosome missing
Duplication Part of a chromosome present twice
Translocation Two chromosomes join long arms or exchange parts

Inversion Segment of chromosome reversed

Isochromosome A chromosome with identical arms
Ring chromosome A chromosome that forms a ring due to deletions in telomeres,
which cause ends to adhere.
 Polyploidy

 Triploid- seedless watermelon and oysters

 Decaploid- a variety of strawberry

 More common in the “lower forms”

 Polyploid animals are often sterile, reproduce by parthogenesis
 Ex. Mole Salamandar- kleptogenesis
 Tetraploid- Salmon
Polyploidy

 The most drastic upset in chromosome number is an entire extra set.

 An individual whose cells have 3 copies of each chromosome is a
triploid (designated 3N, first three sets of chromosomes)
 2/3 of all triploids result from fertilization of an oocyte by two
sperm
 1/3 of cases arises from formation of a diploid gamete such as
normal haploid sperm fertilizes a diploid oocyte.
 Triploid account for 16% of spontaneous abortions.
Aneuploidy

 Cells missing a single chromosome or having an extra one

 Not a good set
 Rarely, aneuploidy have more than one missing or extra
chromosome, indicating defective meiosis in a parent.
Aneuploidy

 Most autosomal aneuploids (with a missing or extra non-sex

chromosome) are spontaneously aborted
 Those that survive have specific syndromes, with symptoms
depending upon which chromosomes are missing or extra
 Mental retardation is common in aneuploidy
 Sex chromosome aneuploidy usually produces milder symptoms
Aneuploidy

 Even though most children are born with the wrong number of
chromosomes have an extra chromosome rather than a missing one.
 Trisomy- extra
 Monosomy- missing
 Most severe that an affected embryo ceases developing
Aneuploidy

 Non-disjunction-the meiotic error that causes aneuploidy.

 Nondisjunction, a chromosome pair fails to separate at anaphase at
either the first or second meiotic division
 This produces a sperm or oocyte that has two copies of a particular
chromosome, or none, rather than the normal one copy
 Different trisomies tend to be caused by nondisjunction in the male
or female at meiosis I or II
Autosomal Aneuploidy

 The most frequent seen extra autosome in newborns are

chromosome 21, 18 and 13.
 These chromosomes carry far fewer protein-encoding genes that
other autosomes
 Extra copies of these chromosomes are tolerated well enough for
some fetuses with them to survive or to be born.
Trisomy 21

 The most common autosomal aneuploidy among live-born

 Characteristics:
 Epicanthal folds- extra folds in the eyelids
 Flat face
 Sir John Langdon Haydon Down- term the condition “mongoloid” 1866.
 Down syndrome is usually short and has straight, sparse hair and tongue
protruding through thick lips.
 90%- non-disjunction during meiosis I (female)
 10%- non-disjunction during meiosis I or II (male)
Trisomy 18

 AKA. EDWARD SYNDROME (John H. Edwards)

 Great physical and mental disabilities (6 month)
 Heart defect, displaced liver, growth retardation and oddly clenched fists.
 Milder signs: overlapping fingers, narrow and flat skull, small mouth and face,
absent/unusual fingerprints, large toes and rocker-bottom feet.
 CaseL Non-disjunction in Meiosis II (oocyte)
Trisomy 18
 Trisomy 13

 AKA. PATAU SYNDROME (Dr. Klaus Patau)

 Signs and symptoms:
 Fusion of the developing eyes (large-eye like structure, small//absent eye)
 Major abnormalities: heart, kidneys, brain, face and limbs, malformed nose,
cleft lip and/or palate in a small head
 Extra finger and toes
Sex Chromosome Aneuploids: Female

 Having extra or missing sex chromosomes

 Less serious than autosomal aneuploids
 Can result from non-disjunction in meiosis
 Sex Chromosome Aneuploids
Situation Oocyte Sperm Consequnce
Normal X Y 46, XY normal male
X X 46, XX normal female
Female nondisjunction XX Y 47, XXY Klinefelter syndrome
XX X 47, XXX triplo-X
Y 45, Y nonviable
X 45, X Turner syndrome
Male nondisjunction X 45, X Turner Syndrome
Meiosis I X XY 47,XXY Klinefelter syndrome
Male nondisjunction X XX 47, XXX triplo-X
Meiosis II X YY 477, XYY Jacobs syndrome
X 45, X Turner syndrome
Male and female non-disjunction XX YY 48, XXYY syndrome
Sex Chromosome Aneuploids: Female

 TURNER SYNDROME (Henry Turner 1938)

 45, X Karyotype
 Also known as XO syndrome
 Sex Chromosome Aneuploids: Female

 TRIPLO X
 47, XXX Karyotype
 Also known as Trisomy X, XXX syndrome
 Symptoms:
Tall stature
Microencephaly
Epicanthal folds
Delayed motor, speech and language development
Learning disabilities- dyslexia
Weak muscle tone
Sex Chromosome Aneuploids: Male

 KLINEFELTER SYNDROME
 47, XXY Karyotype
 Occurs in 1 in 500 male births
 Affected nakes are underdeveloped
sexually
 Most common genetic or chromosomal
cause of male infertility
Sex Chromosome Aneuploids: Male

 JACOB SYNROME
 47, XYY Karyotype
 Occurs 1 in 1,000 male births
 Affected males are apparently normal
 Symptoms:
 Great height
 Acne
 Speech and reading problems
X & Y chromosome
Sexual Development
Genetic Abnormalities
 1. X & Y Chromosomes
X chromosomes Gene Functions
 Metaphase: X-shape ALAS 2 Directs formation of RBC
 Large
ATP7A Regulates coper levels in the body
 150 million base pairs

COL4A5 Required for normal kidney function

DMD Controls muscle function and

pathways between nerve cells

F9 Responsible for normal blood clotting

 1. X & Y Chromosomes
 Y chromosomes
 Pseudoautosomal DNA
 With 50 million base pairs
 Considered as the smallest and least gene-rich human chromosome
 Over half the Y chromosomes is junk DNA (doesn’t code for a
gene at all)
 Individuals with only one X and no Y can survive (Turner
syndrome)
 Male specific region or MSY-lies between two pseudoautosmal
regions
2. Sexual Development

 The phenotype of sex- male and female depend on which type of

gamete an individual produces
 Monoecy- One house
 Dioecious- Two houses
Sex Detemination
 Sex determination is more accurately described as a fate imposed on
ambiguous precursor structures
 Maleness or femaleness is determined at conception, when he inherits an X
and Y chromosome, or she inherits two XX chromosomes
 Mammals starts at an “Indifferent stage:
 4th week: development o genital ridge
 6th week: choice to follow male or female development pathways
 7th week: bipotential or indifferent gonad
Sex Detemination
 If a gene on the Y chromosome called SRY is activated, hormone steer
development follow a male route, in the absence of SRY activation, a
female develops

 Other genes that guide early development (female):

 DAX1- found on the X chromosome gene1
 WNT4- found on chromosome 1
 Other gene that guide early development (male):
 SOX9- leads to development of male gonas, XY males lacking SOX-9 shows sex reveral
to female
3. Genetic abnormalities in Sexual
development
 Hermaphroditism
 Intersex
 Pseudohermaphroditism
 Androgen insensitivity syndome
 5-alpha reductase deficiency
 Congenital adrenal hyperplasia
 3. Genetic abnormalities in Sexual
development
 Androgen insensitivity syndrome
 Causedby mutation in a gene on the X
chromosome
 Absence of receptors for androgens: Testosterone
and Dihydrotestosterone (DHT) stops early
reproductive cell structures from receiving signals

 XY person looks female

3. Genetic abnormalities in Sexual
development
 Individuals whose genetic/chromosomal sex and physical structures, both internal
and external are not consistent with one gender.

 Hermaphroditism- individual with both male and female sexual structure

 Intersex- refers to individuals whose internal structure are inconsistent with

external structures, or whose genitalia are ambiguous.
3. Genetic abnormalities in Sexual
development
 Pseudohermaphroditism- presence of both types of structures but at different
stage of life

 Ex. 5-alpha reductase deficiency- autosomal recessive

 Affective individuals have a normal Y chromosomes, a wild type SRY gene and
testes
 Lack of DHT (Dihydrotestosterone) causes fetus to develop externally as
female- no penis
 5- alpha reductase deficiency
 Changes develop at puberty when the adrenal glands starts
to produce testosterone, so the XY individual who thought
she was female develops masculine features.