Genetics Notes
Genetics Notes
Genetics Notes
Short essays
1. Genetic counselling
Definition: A process of communication and education that addresses concerns relating to the
development and/or transmission of a hereditary disorder.
Goal: To help a patient learn more about the causes of genetic conditions and how they affect
them.
Indications:
o Personal or family history of a genetic condition, birth defect, chromosomal disorder,
or hereditary cancer.
o Two or more pregnancy losses (miscarriages), a stillbirth, or a baby who died.
o A child with a known inherited disorder, a birth defect, mental retardation, or
developmental delay.
o A woman who is pregnant or plans to become pregnant at or after age 35.
o Abnormal test results that suggest a genetic or chromosomal condition.
o An increased risk of developing or passing on a particular genetic disorder on the
basis of a person’s ethnic background.
o People related by blood (for example, cousins) who plan to have children together.
Steps of genetic counselling:
o Diagnosis—based on accurate family history, medical history, examination, and
investigations
o Assessment of risk
o Communication
o Discussion of options
o Long-term contact and support
What happens during a genetic consultation?
o When a person is diagnosed with a genetic condition, the genetics professional
provides information about the diagnosis, how the condition is inherited, the chance
of passing the condition to future generations, and the options for testing and
treatment.
o During a consultation, a genetics professional will:
Interpret and communicate complex medical information.
Help each person make informed, independent decisions about their health
care and reproductive options.
Respect each person’s individual beliefs, traditions, and feelings.
o A genetics professional will NOT:
Tell a person which decision to make.
Advise a couple not to have children.
Recommend that a woman continue or end a pregnancy.
Tell someone whether to undergo testing for a genetic disorder.
2. Aneuploidy
Aneuploidy : Refers to loss or gain of one or more chromosomes
o Monosomy: The absence of a single chromosome is referred to as monosomy.
Monosomy for an autosome is almost always incompatible with survival to term.
Lack of contribution of an X or a Y chromosome results in a 45,X karyotype which
causes Turner syndrome
o Trisomy: presence of an extra chromosome is referred to as trisomy. (eg: Down
syndrome-trisomy 21;Edward syndrome-trisomy 18. Patau syndrome-trisomy 13)
o Tetrasomy: presence of 2 extra chromosome is referred to as tetrasomy.
o Cause for aneuploidy: Results because of Non-Disjunction in meiosis
o Normally the bivalent pair of homologous chromosomes separate during anaphase of
cell division. Failure of separation of one of the pairs of homologous
chromosomes during anaphase is called non-disjunction.
o Non disjunction in meiosis: usually results in trisomy/monosomy/tetrasomy
o
3. X chromosome
The X chromosome is one of the two sex chromosomes in humans (the other is the Y
chromosome).
The sex chromosomes form one of the 23 pairs of human chromosomes in each cell.
The X chromosome spans about 155 million DNA building blocks (base pairs) and represents
approximately 5 percent of the total DNA in cells.
The X chromosome contains 800 to 900 genes that provide instructions for making proteins.
These proteins perform a variety of different roles in the body.
Each person normally has one pair of sex chromosomes in each cell.
Females have two X chromosomes, while males have one X and one Y chromosome. Early in
embryonic development in females, one of the two X chromosomes is randomly and
permanently inactivated in cells other than egg cells. This phenomenon is called X-
inactivation or Lyonization. X-inactivation ensures that females, like males, have one
functional copy of the X chromosome in each body cell. Because X-inactivation is random, in
normal females the X chromosome inherited from the mother is active in some cells, and the
X chromosome inherited from the father is active in other cells.
The following chromosomal conditions are associated with changes in the structure or
number of copies of X chromosome.
o Klinefelter syndrome
o Turner syndrome
o 48,XXYY syndrome
o intestinal pseudo-obstruction
o microphthalmia with linear skin defects syndrome
o triple X syndrome
4. Y chromosome
The Y chromosome is one of the two sex chromosomes in humans (the other is the X
chromosome).
The sex chromosomes form one of the 23 pairs of human chromosomes in each cell.
The Y chromosome spans more than 59 million building blocks of DNA (base pairs) and
represents almost 2 percent of the total DNA in cells.
Each person normally has one pair of sex chromosomes in each cell. The Y chromosome is
present in males, who have one X and one Y chromosome, while females have two X
chromosomes.
The Y chromosome likely contains 50 to 60 genes that provide instructions for making proteins.
Because only males have the Y chromosome, the genes on this chromosome tend to be involved
in male sex determination and development. Sex is determined by the SRY gene, which is
responsible for the development of a fetus into a male. Other genes on the Y chromosome are
important for male fertility.
The following chromosomal conditions are associated with changes in the structure or number of
copies of Y chromosome.
o 46,XX testicular disorder of sex development
o 47,XYY syndrome
o 48,XXYY syndrome
o Y chromosome infertility
5. Sex linked inheritance
Sex-linked inheritance refers to the pattern of inheritance shown by genes that are located on
either of the sex chromosomes.
Types:
a. X linked
i. X linked recessive
ii. X linked dominant
b. Y linked
X linked recessive inheritance: An X-linked recessive trait is one determined by a gene carried on the
X chromosome and usually manifests only in males.
Rules:
Risk calculation
XH : normal
Xh : hemophilic gene
o Examples:
o Haemophilia A (Factor VIII)
o Haemophilia B (Factor IX)
o G6PD deficiency
o Red and green colour blindness
o Duchenne muscular dystrophy (dystrophin)
o Fragile X syndrome
o Becker muscular dystrophy (dystrophin)
o Agammaglobulinaemia (X-linked)
o Ocular albinism
o Hunter syndrome
X linked dominant inheritance: Disorders that are manifest in the heterozygous female as well as in the
male.
Rules:
Risk calculation:
Examples:
Y linked inheritance: Y linked inheritance or holandric inheritance implies that only males are affected.
Rules:
o Y-linked genes are expressed in and transmitted only by males, to all their sons.
Answer:
Answer
Incidence :1:5000
Karyotype: 47,XX,+13 or 47,XY,+13
Clinical features:
o Head and face; Microcephaly with sloping forehead; facial features coarse; cleft lip
and palate; micrognathia
o Eyes: Microphthalmia, anophthalmia, cyclopia or hypotelorism (closely spaced
eyes)
o Hands and feet: Rocker-bottom’ feet; frequently a single palmar crease, postaxial
polydactyly (6th finger present)
o General features: Midline malformations include failure of separation of the
cerebral ventricles, and cardiac abnormalities. Seizures common. Skills limited to
those of a child of 2 years. All boys have undescended testes
Life expectancy : 50% die within the first month, 95% by 3 year
12. Chromosome
Answer:
In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called
chromosomes.
Each chromosome is made up of DNA tightly coiled many times around proteins called
histones that support its structure.
The word chromosome is derived from the Greek [chroma (= color) and soma (= body)]
Morphology of chromosomes
o Chromosomes are not visible in the cell’s nucleus—not even under a microscope—
when the cell is not dividing. However, the DNA that makes up chromosomes becomes
more tightly packed during cell division and is then visible under a microscope.
o At this time each chromosome can be seen to consist of two identical strands known
as chromatids, or sister chromatids,
o These sister chromatids can be seen to be joined at a primary constriction known as the
centromere. Centromeres consist of several hundred kilobases of repetitive DNA and
are responsible for the movement of chromosomes at cell division.
o Each centromere divides the chromosome into short and long arms, designated p (=
petite) and q (‘g’ = grande), respectively.
o The tip of each chromosome arm is known as the telomere. Telomeres play a crucial
role in sealing the ends of chromosomes and maintaining their structural integrity.
o Telomeres consist of many tandem repeats of TTAGGG sequence.
o
Number of chromosomes
o Tjio and Albert Levan described the total number of chromosomes in human beings.
o In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46.
Twenty-two of these pairs, called autosomes, look the same in both males and females.
The 23rd pair, the sex chromosomes, differ between males and females. Females have
two copies of the X chromosome, while males have one X and one Y chromosome.
Classification:
o Morphological: Morphologically chromosomes are classified according to the
position of the centromere.
Metacentric : centromere is located centrally
Acrocentric: centromere is present terminally
Submetacentric: centromere is in an intermediate position
o Denver classification: Based on the three parameters of length, position of the centromere,
and the presence or absence of satellites, divided into group labeled A to G on the basis of
overall morphology
o Group A : 1,2,3. Metacentric except 2 (SM)
o Group B : 4,5. SM
o Group C : 6 – 12, X. SM
o Group D : 13 – 15. AC
o Group E : 16 – 18. SM
o Group F : 19 – 20. M
o Group G : 21,22, Y. AC
13. Sex chromosome
Answer:
o The X and Y chromosomes are known as the sex chromosomes because of their crucial role
in sex determination.
o They are also called as allosomes/gonosomes
o X chromosome:
The X chromosome is one of the two sex chromosomes in humans.
The X chromosome spans about 155 million DNA building blocks (base
pairs) and represents approximately 5 percent of the total DNA in cells.
The X chromosome contains 800 to 900 genes that provide instructions for
making proteins. These proteins perform a variety of different roles in the
body.
Females have two X chromosomes, while males have one X and one Y
chromosome. Early in embryonic development in females, one of the two X
chromosomes is randomly and permanently inactivated in cells other than
egg cells. This phenomenon is called X-inactivation or Lyonization.
The following chromosomal conditions are associated with changes in
the structure or number of copies of X chromosome.
Klinefelter syndrome
Turner syndrome
48,XXYY syndrome
intestinal pseudo-obstruction
microphthalmia with linear skin defects syndrome
triple X syndrome
o Y chromosome:
one of the two sex chromosomes in humans
The Y chromosome spans more than 59 million building blocks of DNA
(base pairs) and represents almost 2 percent of the total DNA in cells.
The Y chromosome is present in males, who have one X and one Y
chromosome, while females have two X chromosomes.
The Y chromosome likely contains 50 to 60 genes that provide instructions
for making proteins.
Because only males have the Y chromosome, the genes on this chromosome
tend to be involved in male sex determination and development. Sex is
determined by the SRY gene, which is responsible for the development of a
fetus into a male.
The following chromosomal conditions are associated with changes in the
structure or number of copies of Y chromosome.
46,XX testicular disorder of sex development
47,XYY syndrome
48,XXYY syndrome
Y chromosome infertility
14. Karyotyping
Answer:
o Chromosomes are conventionally displayed cut out from a photograph or captured from an
electronic image, and arranged as a “paste-up,” with p arms upward, in their matching pairs.
This paired-up presentation is called a karyotype , or karyogram. The procedure to obtain
the photograph is called karyotyping.
o Procedure:
1. Chromosome preparation: to 5 ml of peripheral (venous) blood,
phytohemagglutinin is added, which stimulates T lymphocytes to divide. The cells
are cultured under sterile conditions at 37°C for about 3 days, during which they
divide, and colchicine is then added to each culture. This drug prevents formation of
the spindle, thereby arresting cell division during metaphase. Hypotonic saline is
then added, which causes the red blood cells to lyze and results in spreading of the
chromosomes, which are then fixed, mounted on a slide and stained ready for
analysis
2. Banding: The chromosomes are treated with trypsin, which denatures their protein
content, and then stained with a DNA-binding dye–—also known as ‘Giemsa’–—that
gives each chromosome a characteristic and reproducible pattern of light and dark
bands
3. Karyotype analysis: analysis involves first counting the number of chromosomes
present in a specified number of cells, sometimes referred to as metaphase spreads,
followed by careful analysis of the banding pattern of each individual chromosome in
selected cells.
15. Abnormalities of chromosome
Answer:
o Numerical abnormalities:
i. Aneuploidy : loss or gain of one or more chromosomes
Monosomy: The absence of a single chromosome is referred to as
monosomy. Monosomy for an autosome is almost always
incompatible with survival to term. Lack of contribution of an X or a
Y chromosome results in a 45,X karyotype which causes Turner
syndrome
Trisomy: presence of an extra chromosome is referred to as
trisomy. (eg: Down syndrome-trisomy 21;Edward syndrome-trisomy
18. Patau syndrome-trisomy 13)
Tetrasomy: presence of 2 extra chromosome is referred to as
tetrasomy
ii. Polyploidy: addition of one or more complete haploid complements, known
as polyploidy
Triploidy: presence of multiple of the single haploid number of
chromosomes (eg.69, triploidy)
Tetraploidy: presence of multiple of the 2 haploid number of
chromosomes (eg.92, tetraploidy )
1. Structural: Structural chromosome rearrangements result from chromosome
breakage with subsequent reunion in a different configuration
i. Translocations: transfer of genetic material from one chromosome to
another.
Reciprocal: A reciprocal translocation is formed when a break
occurs in each of two chromosomes with the segments being
exchanged to form two new derivative chromosomes.
Robertsonian: A Robertsonian translocation is a particular type of
reciprocal translocation in which the breakpoints are located at, or
close to, the centromeres of two acrocentric chromosomes.
ii. Deletions: A deletion involves loss of part of a chromosome and results in
monosomy for that segment of the chromosome. A very large deletion is
usually incompatible with survival to term, and as a general rule any deletion
resulting in loss of more than 2% of the total haploid genome will be lethal.
Answer:
o Normally the bivalent pair of homologous chromosomes separate during anaphase of cell
division. Failure of separation of one of the pairs of homologous chromosomes during
anaphase is called non-disjunction.
o Non disjunction in meiosis: usually results in trisomy/monosomy/tetrasomy
Answer:
This condition derives its name from Dr. Langdon Down, who first described it.
Karyotype: 47,XX,+21 or 47,XY,+21 (Trisomy 21)
Incidence : 1 in 700
Clinical features:
o Head and face: Small, flattened head, short neck with excess nuchal skin. Face
broad. Tongue without a central fissure. Low nasal root, ears small.
o Eyes: Eyes slanting upwards, with marked epicanthic folds; cataracts, squint and
nystagmus (involuntary eye movements). Most have white speckles on the iris.
o Hands and feet: Half have a single palmar flexion crease (Simian crease). Limbs
and fingers short, little finger in-turned, with single crease. Large ‘sandal gap’.
Webbing of toes 2 and 3.
o Muscle tone: Babies are always ‘floppy’ (hypotonic) and tend to be sleepy.
o IQ: intellectual delay
o Cardiac: Atrial and ventricular septal defects, common atrioventricular canal, patent
ductus arteriosus
o Other features: Anal atresia, duodenal atresia, Hirschsprung disease, short stature,
strabismus
o Life expectancy: 50–60 years
The hands of an adult with Down syndrome. Note the single palmar crease in the left hand plus
bilateral short curved fifth fingers (clinodactyly).
18. Klinefelter’s syndrome
Answer:
1. X chromosome
The X chromosome is one of the two sex chromosomes in humans (the other is the Y
chromosome).
The X chromosome spans about 155 million DNA building blocks (base pairs) and represents
approximately 5 percent of the total DNA in cells.
The X chromosome contains 800 to 900 genes that provide instructions for making proteins.
Females have two X chromosomes, while males have one X and one Y chromosome. Early in
embryonic development in females, one of the two X chromosomes is randomly and
permanently inactivated in cells other than egg cells. This phenomenon is called X-
inactivation or Lyonization. X-inactivation ensures that females, like males, have one
functional copy of the X chromosome in each body cell.
The following chromosomal conditions are associated with changes in the structure or
number of copies of X chromosome.
o Klinefelter syndrome
o Turner syndrome
o 48,XXYY syndrome
o intestinal pseudo-obstruction
o microphthalmia with linear skin defects syndrome
o triple X syndrome
o other chromosomal conditions
2. Y chromosome
The Y chromosome is one of the two sex chromosomes in humans (the other is the X
chromosome).
The Y chromosome spans more than 59 million building blocks of DNA (base pairs) and
represents almost 2 percent of the total DNA in cells.
The Y chromosome is present in males, who have one X and one Y chromosome, while females
have two X chromosomes.
The Y chromosome contains 50 to 60 genes that provide instructions for making proteins.
Because only males have the Y chromosome, the genes on this chromosome tend to be involved
in male sex determination and development. Sex is determined by the SRY gene, which is
responsible for the development of a fetus into a male. Other genes on the Y chromosome are
important for male fertility.
The following chromosomal conditions are associated with changes in the structure or number of
copies of Y chromosome.
o 46,XX testicular disorder of sex development
o 47,XYY syndrome
o 48,XXYY syndrome
o Y chromosome infertility
3. Genetic counselling
Definition: A process of communication and education that addresses concerns relating to the
development and/or transmission of a hereditary disorder.
Indications:
Personal or family history of a genetic condition, birth defect, chromosomal disorder, or
hereditary cancer.
Two or more pregnancy losses (miscarriages), a stillbirth, or a baby who died.
A child with a known inherited disorder, a birth defect, mental retardation, or
developmental delay.
A woman who is pregnant or plans to become pregnant at or after age 35.
Abnormal test results that suggest a genetic or chromosomal condition.
An increased risk of developing or passing on a particular genetic disorder on the basis of
a person’s ethnic background.
People related by blood (for example, cousins) who plan to have children together.
Steps of genetic counselling:
a. Diagnosis—based on accurate family history, medical history, examination, and
investigations
b. Assessment of risk
c. Communication
d. Discussion of options
e. Long-term contact and support
8. Satellite bodies
In acrocentric chromosomes, distal to the secondary constriction small segment of the
chromosome is present. This segment is called satellite body.
Chromosomes bearing satellites are called SAT-chromosomes
In humans chromosome 13,14, 15, 21, 22 and Y chromosomes have satellite bodies.
9. Anaphase lag
Normally during cell division the chromosomes separate during the anaphase. This is
called as disjunction.
Failure of this separation is known as non-disjunction
Delay in the process of the separation is known as “anaphase lag”
Anaphase lag and non-disjunction are the causative factors for aneuploidy.
Secondary constriction
conconstriction
12. Name the chromosmes with satellite bodies
Acrocentric chromosome have terminal structures called as satellite bodies. Hence are
also called as satellite chromosomes.
Examples:
i. Group D : chromosome 13-15
ii. Group F: chromosome 21, 22 and Y chromosome
o Denver classification: Based on the three parameters of length, position of the centromere,
and the presence or absence of satellites, divided into group labeled A to G on the basis of
overall morphology
o Group A : 1,2,3. Metacentric except 2 (SM)
o Group B : 4,5. SM
o Group C : 6 – 12, X. SM
o Group D : 13 – 15. AC
o Group E : 16 – 18. SM
o Group F : 19 – 20. M
o Group G : 21,22, Y. AC
23. Chromosomes
In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called
chromosomes.
Each chromosome is made up of DNA tightly coiled many times around proteins called
histones that support its structure.
The word chromosome is derived from the Greek [chroma (= color) and soma (= body)]
Morphology of chromosomes
o Chromosomes are not visible in the cell’s nucleus—not even under a microscope—
when the cell is not dividing. However, the DNA that makes up chromosomes becomes
more tightly packed during cell division and is then visible under a microscope.
o At this time each chromosome can be seen to consist of two identical strands known
as chromatids, or sister chromatids,
o These sister chromatids can be seen to be joined at a primary constriction known as the
centromere. Centromeres consist of several hundred kilobases of repetitive DNA and
are responsible for the movement of chromosomes at cell division.
o Each centromere divides the chromosome into short and long arms, designated p (=
petite) and q (‘g’ = grande), respectively.
o The tip of each chromosome arm is known as the telomere. Telomeres play a crucial
role in sealing the ends of chromosomes and maintaining their structural integrity.
o Telomeres consist of many tandem repeats of TTAGGG sequence.
Number of chromosomes
o Tjio and Albert Levan described the total number of chromosomes in human beings.
o In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46.
Twenty-two of these pairs, called autosomes, look the same in both males and females.
The 23rd pair, the sex chromosomes, differ between males and females. Females have
two copies of the X chromosome, while males have one X and one Y chromosome.
Y chromosome:
i. Belongs to group G and is acrocentric in type
ii. The Y chromosome spans more than 59 million building blocks of DNA (base
pairs) and represents almost 2 percent of the total DNA in cells.
iii. The Y chromosome likely contains 50 to 60 genes that provide instructions for
making proteins.
iv. Because only males have the Y chromosome, the genes on this chromosome tend
to be involved in male sex determination and development. Sex is determined by
the SRY gene, which is responsible for the development of a fetus into a male.
v. The following chromosomal conditions are associated with changes in the
structure or number of copies of Y chromosome.
1. 46,XX testicular disorder of sex development
2. 47,XYY syndrome
3. 48,XXYY syndrome
25. Autosomes
Human beings have 46 chromsomes which are arranged as 22 pairs of sutosomes and 1
pair of allosmes/sex chromsomes
Chromosome 1-22 are called as autosomes.
Autosomes are essential for life. Loss of even one autosome is fatal
Gain of 1 or 2 autosomes is called as trisomy and tetrasomy respectively.
26. Define chromosome. Give the chromosomal complement of normal male and female
A chromosome is a large macromolecular complex comprising a single molecule of DNA
and multiple proteins.
Chromosomal complement
o Normal male: 46,XY
o Normal Female: 46, XX
27. Karyotype
The chromosome constitution of an individual is known as a karyotype.
This term is also used to describe a photomicrograph of an individual’s chromosomes,
arranged in a standard manner.
28. Karyotyping
The procedure of obtaining karyotype of an individual is known as karyotyping.
29. Write any 3 differences between mitosis and meiosis
Mitosis Meiosis
36. Monosomy
Monosomy refers to Absence of a single chromosome
Monosomy of autosomes is incompatible with life
Monosonmy of Allosomes – Turner’s syndrome
Cause for monosomy- non disjunction during meiosis
37. Trisomy
Trisomy refers to Presence of an extra chromosome
Examples:
i. Trisomy 21 / Down’s syndrome
ii. Trisomy 13/ Patau syndrome
iii. Trisomy 18/ Edward syndrome
Cause for trisomy : Non disjunction