CHROMOSOME

Introduction & Structure:

In the nucleus of each cell, the DNA molecule is packed into thread like structures called
Chromosomes. Each chromosome is made up of DNA tightly coiled many times around
protein called histones that support its structure. 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 become more tightly packed during cell division and
is then visible under a microscope. Most of what researchers know about chromosome
was learned by observing chromosomes during cell division. Each chromosome has
constriction point called Centromere, which divides the chromosome into two sections
or “arms”. The short arm of chromosome is labeled the “p arm”. The long arm of
chromosome is labeled the “q arm”. The location of centromere on each chromosome
gives the chromosome its characteristic shape, and can be used to help describe the
location of the specific genes.
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, differs between males and females.
Females have two copies of the X chromosome, while males have one X and one Y
chromosome.

DNA: Deoxyribonucleic Acid

DNA is largely confined to the nucleus and is the main component of the chromosomes.
It is also called nuclear DNA.
Quantity: The DNA content is fairly constant in all the cells of a given species. Just
before cell division, the amount of DNA is doubled. The gametes have half the amount of
DNA as they contain half the number of chromosomes.
Chemical Structure: Chemical structure of DNA was explained by P.A. Levene.
DNA is the largest macromolecule in the organisms. It is long double chain of
deoxyribonucleotide units. The two deoxyribonucleotide chains are twisted around a
common axis to form a right-handed double helix (spiral) that encloses a cylindrical
space in it. Each deoxyribonucleotide unit consists of three different molecules
Phosphate, a 5-Carbon deoxyribose sugar and a Nitrogenous base. The nitrogenous base
may be a 9-membered double ringed purine i.e. Adenine (A) or Guanine (G) or a 6-
membered single ringed pyrimidine i.e. Thymine (T) or Cytosine (C).The nitrogenous
base molecules are joined to sugar molecule at 1-Carbon position by glycoside bonds and
project to space enclosed in the helix at about 90 degree to the long axis of the helix. The
two deoxyribonucleotide chains are held together by hydrogen bonds. Adenine of one
chain is always joined to thymine of other chain by two hydrogen bonds. Cytosine of one
chain is always linked to Guanine of the other chain by three hydrogen bonds.
Watson and Crick Model:
J.D Watson, an American biologist & F.H.C Crick, an English Chemist, in 1953
suggested a model of DNA molecule to explain its structure. This model got them the
1962 Nobel Prize. Acc. to Watson & Crick, the DNA molecule consists of two long,
parallel chains (strands) which are joined together by short crossbars at regular intervals.
The two chains are spirally coiled around a common axis in a regular manner to form a
double helix. The double helix is of constant diameter. The bases face the interior of the
double helix where as the sugar and phosphate components form backbones on the
outside. The helix is generally right- handed, that is, the turns run clockwise looking
along the helical axis.
Some Important Points Regarding DNA:
 Human DNA is double stranded helical structure comprised of four different
bases, the sequence of which codes for the assembly of amino acids to make a protein
e.g. an enzyme. These proteins are important for following reasons:
a) For body characteristics such as eye color.
b) For biochemical processes such as the gene for the enzyme that digests
phenylalanine.
c) For body structure such as chromosome collagen gene important for bone
formation.
d) For cellular functioning such as genes associated with cell cycle.
 The four DNA bases are Adenine, Guanine, Cytosine, Thymine or AGTC. It is
these four compounds can be arranged in countless sequences and it is the sequence in
which ours are arranged which determines who and what we are.
 A change, or mutation, in the coding sequence, such as duplicated or deleted
region or even a change in only one base, can alter the production or functioning of the
gene or gene product, thus affecting cellular processes, growth & development.
 DNA analysis can be done on almost any body tissue (blood, muscle, skin) using
molecular techniques (not visible under microscope) for mutation analysis of a specific
gene with a known sequence for DNA linkage of genetic markers associated with a
particular gene.

GENES:
Introduction: In 1865, Gregor Mendal was the first to describe the elements of
heredity i.e. Genes. His observation and analysis of the observable features of Pea led
him to conclude that specific traits were passed on unchanged from a parent plant to the
next generation.
Definition: Gene is a Greek word which means ‘to become’ or ‘to grow into’. Genes,
which are made up of DNA, acts as RNA instructor to make molecules called Proteins.

In humans, genes vary in size from a few hundred DNA bases to more than 2
million bases. Most of the genes are same in all people, but a small number of genes are
slightly different between people.
CHARACTRISTICS:
 Genes are the true carriers of heredity, responsible for the development ad
structure of human body. They are the physical substances passed on from parent to
child. The parents’ genes, in turn, have come from their parents, grandparents, and other
more distant ancestors.
 Some of the genes are dominant- they produce the trait in every generation. Other
genes are recessive- produce trait that skips several generations.
 Genes do not act alone; rather they are influenced by the genetic background of an
individual and by external and internal environment.
 Each human nucleated somatic cell has about 30,000 genes in the nucleus. Cells
also have some non-nuclear genes located within the mitochondria within the cytoplasm.
 Alternate forms of a gene are termed as alleles.
 For each gene, an individual receives an allele from each parent, and thus has two
alleles for each gene on the Autosomes and also on the X chromosomes in the females.
 Males have only one X chromosome and therefore have only one allele for all
genes on the X chromosome. They are hemizygous for all X linked genes.
 At any autosomal locus, or gene site, an individual can have two identical alleles
(homozygous) for that locus or can have different alleles (heterozygous) at a particular
locus e.g. for eye color.
 Genotype refers to the constitution of genetic material of an individual; for
practical purpose it is commonly used to address a specific pair e.g. the gene of sickle cell
anemia, gene for cystic fibrosis etc.

Approaches to Common Genetic Disease:

Prenatal testing and screening are part of routine antenatal care. It may be as simple as
ultrasound or blood test or as complex as percutaneous umbilical blood sampling or fetal
tissue sampling.
Purpose: The purpose of prenatal tests is to determine whether there is a problem with
fetal growth and development.
Types: Tests are categorized into two types:
 Non-Invasive
 Invasive

Non-invasive Prenatal Testing:

1. Ultrasound: Ultrasound has become the standard in fetal evaluation because it is

safe and non invasive.
Indications: It can confirm:
 Pregnancy.
 Fetal Age.
 Growth & Development.
 Placental implantation site.
 Fetal viability or death.
 Multiple gestations.
 Amniotic fluid volume.
 Placental calcification.
 Facilitate the use of more invasive studies, diagnostics and treatment.

Procedure: Clients are instructed to consume approximately 32 to 48 oz of fluid 1 to 2

hours before the procedure and are not encouraged not to void until the procedure is
completed. Some discomfort due to the pressure exerted by the transducer over a full
bladder is expected. A full bladder is typically not necessary for clients in the late stages
of pregnancy.

FETAL ECHOCARDIOGRAMS:
Fetal echocardiograms are performed through the maternal abdomen when there is
suspicion of congenital cardiac defect. This procedure provides information regarding
blood flow velocity and direction, size, position, valves, and chambers of the heart. No
specific patient preparation is necessary and no discomfort is involved in the procedure.

Computerized Tomography (CT) and MR Imaging:

CT and MR Imaging can be used during pregnancy. Concern has been raised as to the
long term side effects, particularly with MRI due to the high noise level transferred to the
fetus. Risks of the technology and the lack of a long history of its use must be weighed
against the benefits of determining a problem in utero.

INVASIVE PRENATAL TESTING:

Serum Alpha-fetoprotein (AFP) & Triple Screens:
Maternal serum AFP screening is used routinely to assess for neural tube defects. AFP
screening involves obtaining a venous sample of maternal blood. Screenings are usually
performed between 16 & 18 weeks’ gestation.
Indications:
Elevated AFP level:
o Neural tube defect.
o Multiple gestations.
o Rh Incompatibility.
o Low gestational age.
o Congenital abnormalities- congenital nephrosis, duodenal atresia, tetrology of
fallot etc.
Low AFP level:
o Trisomy-13, 18, 21
Triple Screening:
The determination of AFP levels is also done in conjunction with triple marker
screening. This consists of testing for AFP, Human Choronic Gonadotropin, and Serum
Estriol levels.
Indication:
o Trisomies.

Amniocentesis and Chorionic Villus Sampling:

Two parental screening tests are used to assess fetal karyotype (the actual picture of the
fetus’ chromosomes) abnormalities: amniocentesis and chorionic villus sampling (CVS).
Both tests are use to diagnose trisomies 13, 18, 21 and neural tube defects. They also can
assess for abnormal AFP levels, glucose levels and other substances found in the
amniotic fluid or fetal tissue.
Amniocentesis:
Indications:
 Carriers of metabolic or autosomal recessive disorder.
 Maternal age > 35 yrs
 Maternal history of infertility, still births or multiple spontaneous abortions.
 A previous child with chromosomal abnormalities.
 Neural tube defects or congenital anomalies.
 Family history of- parental balance translocation, mental retardation.
 Teratogen exposure before or during pregnancy.
 Abnormal AFP or Ultrasound Results.
Procedure:
Amniocentesis involves the insertion of a needle through the maternal abdominal and
uterine walls and into the amniotic space. Approximately 20- 30 ml of amniotic fluid is
aspirated. The procedure is performed under ultrasound guidance at approximately 16 to
20 weeks gestation. Fetal cells are retrieved for analysis. Results take approximately 10to
20 days.

Chorionic Villus Sampling:

CVS is performed in the first trimester between weeks 0-12 but most commonly after 8
weeks gestation. It provides the earliest diagnosis of a fetal problem. Any candidate for
amniocentesis is generally a candidate for CVS. The procedure is performed under
ultrasound guidance, either transabdominally or transcervically depending upon placental
position. However any woman with active type-1 genital herpes must undergo
transabdominal CVS.
Procedure:
The test involves the removal, by gentle suction, of a sample of fetal tissue from the villi
of the chorion, actual fetal tissue that anchors the fetus to the uterine wall.
Advantages over Amniocentesis:
Two advantages of CVS over Amniocentesis:
 It can be performed early in the gestation.
 The direct examination of fetal cells can be done.
Indications:
 Chromosomal or single gene problems.
 Metabolic or hematological problems.
Contraindications:
 Isoimmunized clients.
Risks:
 Can not measure AFP level.
 Offers no information regarding neural tube defects.
 Fetal loss.
 Limb reduction.

PERCUTANEOUS UMBLICAL BLOOD SAMPLING:

PUBS permit the removal of blood from the fetal placental circulation. Because it is less
risky, it has replaced fetoscopy and virtually has revolutionized our ability to assess,
evaluate and threat the fetus in utero by direct venous assess.

Procedure:
It can be performed as early as 16 to 18 weeks’ gestation or up to term providing there is
accurate cord visualization. Test results are obtained in 48 to 72 hours. The procedure
entails passing a spinal needle through the maternal abdomen and uterine wall and into
umbilical cord vessels under high resolution ultrasound guidance. A blood sample is
aspirated into a heparinized syringe. The preferred testing site is the placental cord
(chordocentesis).Fetal-abdominal cord and free loops of cord are also acceptable.
Indications:
o Rapid karyotyping.
o The diagnosis and treatment of fetal anemia.
o Fetal infection.
o Severe red blood cell alloimmunization.
o Erythroblastosis fetalis.
o Non-immune fetal hydrops.
o Inherited disorders.
o Thrombocytopenia.
o Evaluation of thyroid function.

FETAL TISSUE SAMPLING:

Fetal Tissue Sampling is indicated for disorders that are not diagnosable through
amniocentesis or CVS and are increased risk for congenital anomalies. The procedure
may be performed at16 to 22 weeks’ gestation.
Indications:
Skin specimen about 2 mm in diameter typically is taken from the buttocks, back, thorax
and occasionally from scalp. Liver biopsy in case of liver enzyme abnormalities, muscle
biopsy when DNA analysis is inconclusive is done.

Procedure:
Fetal tissue sampling is done under the guidance of ultrasound with the client mildly
sedated in order to decrease fetal movements.
Risks:
Spontaneous abortions.
Amniotic fluid leakage.
Maternal or fetal infection or injuries.
Preterm labor or delivery.
Hemorrhage to anterior abdominal wall.
Uterine or placental injuries.
Cosmetic or functional injuries.
BIBLIOGRAPHY:
 Suresh Kumar Sharma “Human Genetics in Nursing” Ed 1 st,
Published by Jaypee Brothers, pp-1-4, 69-78.
 P.S Dhami, H.N. Shrivastava “Textbook of Biology” Ed 4 th,
Published by Pradeep Publications, pp- 36-63.
 Howkins & Bourne “Shaws Textbook of Gynaecology” Ed 13 th,
Published by Elsevier,pp- 93,71,265-268.
 www.google.com