CHROMOSOMES, GENES AND DNA

Please note that Klug and Cummings (2000) provide more detailed
information about the material presumed in this section.
Each chromosome is a long thread-like structure made up of one DNA
molecule with many proteins associated with it. It has many genes arranged in a
fixed manner, one after the other throughout its length (Fig. 12.1).

In the DNA molecule, the uphrights are made of alternating sugar residue and
phosphate groups (the sugarphoshate back bone) and the rungs are composed of
organic bases, cach rung consisting of two bases. There are four different bases;
two purine bases-adenine (A) and guanine (G); and two pyrimidine bases-cytosine
(C) and thymine (T). each rung is made up of a pair of bases, one purine and one
pyrimidine, and the pairing arrangements in theses rungs are very specific:
Adenine always pair with thymine
Guanine always pairs with cytosine
The information stored DNA is useless unless it can be decoded and used
to make cellular and organismal components. The process of decoding and using
the information stored in DNA is usually referred to as the process of gene
expression. Most commonly, the stored information in DNA is used to direct the
production of proteins. There are literally thousand of different proteins as
collagen in tendons, transport protein such as hemoglobin in the metabolism of
the cell and organism. Any protein is made up of amino acids joined together in a
chain and cach protein has its own amino acid sequence which determines its
function.
The encoding of information on a DNA inolecule is achieved by
specifying the precise order (sequence) of the organic bases along the molecules
length. For example, the sequence AAGCTGTCC would encode a certain piece of
information; the sequence GTACTCCTA would incode another, different, piece of
information.
The information stored in DNA is decoded using two processes
transcription and translation. In transcription (which takes place in the nucleus),
part of a DNA molecule is used as a template to produce a molecule of messenger
RNA (mRNA) and this mRNA then undergoes translation (on the ribosomes in
the cytoplasm of the cell) to produce the protein specified ultimately by the DNA
(Fig. 12.3).
Ribonucleic acid (RNA) is the other kind of nucleic acid found in the cell.
Unlike DNA, it is single-stranded and it also contains the pyrimidine base uracil
in place of rhymine. There are three different forms of RNA wound in the cell,
and all of these are involved in the decoding of information from DNA. These
forms are; mRNA; rRNA (ribosomal RNA-a major component of the ribosome)
and tRNA (transfer RNA-curcial in translation as an adaptor molecule between
mRNA.

THE HUMAN GENOME

The entire genetic complement of a cell or organism is refereed to as its
genome. Within the nucleus of all nucleated human cells (apart from developing
and mature gametes) there are 46 chromosomes thus the human genome consists
of 46 chromosomes. These chromosomes are arranged in 23 pairs (known as
homologous pairs) and within each of these pairs, one member is lerived from the
father, the other from the mother. One of these p[airs consists of the sex
chromosomes in the female, this pair consists of two X chromosomes, in the male
it consists of one X and on Y chromosome. The remaining pairs are collectively
known as autosomes and the chromosomes in them are numbered by length, No. 1
being the longest and no. 22 the shortest.
It now seems most probable that the human genome contains some 30.000
genes altogether, a far smaller number than had previously been suggested, e.g.
100.000-150.000 (Nicholl, 2002).

CELL DIVISION
There are two different types of cell division:
Mitosis, which leads to the production of two daughter cells identical in
chromosomes number to the parent cell (46 in humans, fig. 12.4).
 Mitosis, which also leads to the production of two daughter cells, but each
containing only half the number of chromosomes of the parent cell (23 in
humans; fig. 12.5).
Mitosis occurs extensively during embryonic and fetal development to increase
cell numbers, and also occurs in the adult in tissues where cells are routinely lost
(e.g. tie skin; epithelium of the gastrointestinal tract) and in the repair processes
that occur following tissue damage. Meiosis only occurs during the production of
gametes in the gonads and the reduction in chromosome number that it includes is
essential if sexual reproduction is to take place without doubling the amount of
genetic material in each generation. Note that some rearrangement of genetic
material (e.g. exchange of corresponding chromosomal segments crossing-
over) can occur during meiosis. This is an important part of the genetic variation
that is an essential feature of sexual reproduction (Fig. 12.6).
Copying (replication) of DNA occurs during both mitosis and meiosis and
it is clearly of great importance that this occurs accurately, so that errors are not
introduced into the DNA, with possible consequent changes in the structure and
function of an encoded protein (Nairne, 1993). One very important way in which
this is ensured is by the semi-conservative mechanism of DNA replication: a
parental DNA molecule separetes into its two component strands and each of
these is then used as a template for the assembly of a new strand. The Strict rules
of base-pairing (A always pairing with T G always pairing with C) ensure that
each new stranded molecule is an exact copy o the parent molecule (see Fig.
12.21.
It is also important to ensure that chromosomes move correctly into the
daughter cells during cell division if they do not, there can be very serious
consequences.
The study f chromosomes is called cytogenetic, and chromosomes are
usually isolated from lymphocytes. Cells in skin or muscle biopsies, or bone
marrow cells of the relative accessibility of these cell types.
If there are too many or too few chromosomes present after fertilization
has taken place (usually the result of a failure of chromosomes to move correctly
into the daughter cells during meiosis), or if there is some alteration in their
structure, the pregnancy may result in miscarriage or an abnormal fetus. By and
large, anomalies that involve whole chromosomes, or large pieces of
chromosomes are likely to have very serious effects (e.g. embryonic or fetal
death) as these are very major genetic abnormalities. In fact, it has been shown
that the majority of severe chromosomal abnormalities are not compatible with
normal development, and thus embryos with such defects die at an early stage of
development. e.g. approximately 15% of pregnancies terminate in spontaneous
abortion, and about 50% or theses are chromosomally abnormal (Lockwood,
2000).
Several different types of chromosomal anomaly are known:
The presence of three chromosomes of one type (e.g. three chromosomes 18)
is called trisomy
The presence of just one member of a pair is called a monosomy
a structural change arising from the loss of a piece of a chromosome is known
as a deletion
when a part of a chromosome breaks off and is added to another chromosome,
it is called a translocation
a reciprocal translocation occurs if two chromosomes exchange fragments
with each other
The commonest chromosomal birth anomaly is Downs syndrome, where
there are 47 chromosomes instead of 46 (termed trisomy 21 three copies of
chromosome 21). The incidence is 1.5 per 1000 live births and this figure rises
with maternal age (Harper. 1993. Most children with Downs syndrome, however,
are born to women under 30 years of age, simply because more women under 30
give birth. Some children with Downs syndrome (1 in 20) have only 46 separate
choromo-somes, because the extra chromosome 21.5 mined to another in the form
of a translocation. In such eases, it is important to examine the parents genetically,
because one of them may carry this translocated chromosome in a balanced
fashion, having the correct amount of generic material, but only 45 separate
chromosomes. Such a parent is at high risk of having another child with Downs
syndrome.
There are only two other examples of trisomies that are consistent with life
trisomy 13 and trisomy 18 and even in these cases, the defects are many and
severe, and affected individuals typically survive for only a few months, after
birth.
Other common chromosomal anomalies occur among the sex
chromosomes, e.g. 1.3e of implanted conceptions may carry one X-chromosome
without a Y or second X (monosomv X, Turners syndrome the only viable
human monosomy). Very few of these fetuses survive about. 0.4 per 1000 live-
born girls. More common at birth are other anomalies such as XXX (0.65 per
1000 girls), XYY and XXY (1.5 per 1000 boys Klinefelters syndrome; Harper,
1993). These sex chromosome anomalies, however, generally produce fewer ill-
effects than the autosomal anomalies, though these effects can still be serious for
the affected individual.
Genetic characteristics unclosing genetically determined deseases) can be
inherited in one of four ways:
1. autosomal dominan inheritance
2. autosomal receasive inheritance
3. sex-linked dominant inheritance
4. sex-linked recessive inheritance.
Note that the usual patterns of dominance and recesiveness do not apply in
the cases of genes carried on the sex chromosomes see below.
Common types of genetic disease include:
enzyme deficiency states (inborn errors of metabolism). if due to a mutation
(change) in an auto. somal gene, these are very often recessive in terms of
their inheritance pattern, because many metabolic proceses can proceed at an
adequate rate with reduced levels of enzymes
defects in structural proteins (e.g. in connective tissue): these arc, however,
often inherited as dominant conditions, as reduced levels of these proteins are
often insufficient to avoid the appearance of pathological effects.

Autosomal characteristics/diseases
 Most human generic diseases are due to mutations (alterations) in
autosomal genes, simply because that there is much more genetic material in total
in the 22 pairs of autosomes than in the single pair of sex chromosomes.
Remember that a recessive allele of an aurosomal gene is expressed only if
its counterpart on the homologous chromosome is the same (i.e. the homozygous
state), while a dominant allele of an autosomal gene will be - expressed whatever
the nature of its counterpart on the homologous chromosome (hetero- or
homozygous state.
Clearly a homozygous person can only trans one type of allele (normal or
mutant) to any child he or she may have. A heterozygous person (sometimes
referred to as a carrier), however, can, equally clearly transmit either a normal or
an abnormal allele to a child. Just which allele a heterozygous parent transmits in
any particular case is a random event, so there 1 in 2 (50%) chance of the child
inheriting either allele form such a parent. Thus, overall, the following situations
can arise:
if both parents are homozygous for the same allete (dominant or recessive),
then all their children will also be homozygous for that allete (Fig. 12.8).
if one parent is homozygous for one allele (e.g. dominant) and the other parent
homozygous for the other allele (e.g. recessive), then all their children will be
heterozygous (fig.12.9)
These inheritance patterns have abvious consequences for the frequencies
of characteristics/ disorders inherited from parent of these different genetic types.
Thus whilst both autosomal dominant and recessive charactistics/diseases occur in
both males and females, dominant characteristics tend to be present in each
generation of an affected family, whilst recessive ones do not typically occur in
cach generation. This difference rises because (uless a new mutation has occurred)
a recessive characteristic can only be seen in the children of a heterozygote and
ether an affecred individual or another heterozygote. And if the particular
recessive characteristic is rarc, the probability of this happening is quire small. In
practice, it is often found that parents of an individual affected by a rate recessive
characteristic are related to cach other (e.g. first cousins); such consanguineous
matings are more likely to bring together two heterozygote. An exception to this
general rule is the case where the relevant is cystic fibrosis 1 in 22 Britons carry
an allete3 that can cause this disease.
Rarely child is born with a dominant characteristic/ disorder but
subsequent investigations show that nether parent carries the relevant mutant
allele. In suhc a case, the allele must have arisen as a result of a new mutation
(during the process of gamete formation in one parent) and thus the chance of a
second child being born with the same disorder is very low. When the affected
child comes to have children however, the risk of him or her transmitting the
mutant allele will clearly be 50% again.
It is theoretically possible for a child to be born with a recessive
characteristic/disorder and for neither parent to carry the relevant mutant allele.
However, for this to happen, there must be mutations in the same gene during
gamete production in both or the parents and, in practice, the chances of this
happening are very low indeed. Clearly, such a child would always transmit the
mutant allele to any children that he or she had.)
Further problems arise with diseases in which the disease process is either
very variable in its severity (e.g. myotonic dystrophy) or does not become
apparent until later in life (e.g. Huntingtons disease). In the first case, it is
possible for people to have and transmit the disease without suffering any serious
ill-effects themselves, (although subtle signs of such diseases can often be
detected it sought). In the second, many sufferers have had their familier before
before they realize they carry a mutant allele, In ether case, parents may
unknowingly pass on mutant alleles to their children and thus have several
affected children.
Examples of recessively inherited autosomal conditions include
phenylketonuria, galactosaemia and cystic fibrosis; examples of dominantly
inherited autosomal conditions include achondroplasia, Marfans syndrome and
Huntingtons disease.

Sex-Linked characteristics/diseases
Sex-linked conditions are those for which the relevant genes are carried on
the sex chromosomes. They are more complex in their inheritance patterns than
autosomal, characteristic because of the genetic difference between men and
women, women having two X chromosomes in each cell, and men having one X
chromosome and one Y chromosome.
Obviously, there are genes on both the X and Y chromosomes and hence
both X-linked and Y-linked characteristic are known. In practice, however there
are very few genes on the Y chromosome (which is very small) and there are thus
very few Y-linked characteristics. As result of this, Y-linked characteristics are
seldom considered and the terms X-linked and sex-linked are often used
interchangeably (though this is, strictly speaking, incorrect). Note that the genes
carried on the two sex chromosomes are quite different.
Only one of the two X chromosomes is active in any cell in a womans
body, the other is inactive (a Barr body). Which X is inactive in any one cell is
random, and differs throughout the cells of the womans body.
A very important consequence of the difference in sex chromosome
complement between men and women is that men will always exhibit a
characteristic caused by a recessive allele that they carry on their X chromosome
since they do not have a second X chromosome chat can carry the corresponding
dominant allele to hide the presence of the recessive allele. With respect to
women can be homozygous dominant or recesive or heterozygous for any gene on
the X chromosome. Thus a woman will only exhibit a recessive X-linked
characteristic if she is homozygous recessive. In practice, since this means that
such a woman must be the child of a father who exhibits that characteristic and
ether acarrier mother or a mother who also exhibits hat characteristic, and since
these combination of parents are rare, such woman are, in turn, very rare.
Both X linked dominant and recessive characteristics/ diseases are known
and their patterns of inheritance can be summarized as follows:
In X-linked recessive inheritance, there is never maleto-male transmission of
the characteristic, since a father must pass on his Y chromosome if the child is
to be male. Also, as explained above, it is most usual to sc only males affected
by the condition.
In X-linked dominant inheritance, the pattern 1ooks very much like that for an
autosomal dominant trait. However, because the mutant allele is carried on the
 X chromosome, an affected male cannot pass it on to this sons; however; all
of his daughters will be affected. Thus, there is an excess of affected females.
Among the best-known examples of X-linked recessive diseases are Duchcenne
muscular dystrophy, red/green colour-blindness and the haemophilias. There are
only a few X-linked dominant diseases, one example being hyposphosphatemic
(vtamin D-resistant) rickets.

Polygenic And Multifactorial Characteristics

For some traits and diseases, it is clear that individual genes are solely
responsible, but much evidence is emerging that, in many cases, gens work
together. It is there tore not only important to understand the particular role of
individual genes, but also their location and their relationship to other genes
(Judson, 1993).
Many inherited characteristics/ diseases are influenced by several genes
father than just one or two. Such characteristic are said to be polygenic, and the
details of their inheritance patterns are often difficult to define precisely owing to
the interplay between the different alleles of the various genes involved.
Polygenic inheritance should not be confused with situation here several
genes/disorders can cause the same effect e.g. blindness. There are many different
inherited conditions that cause blindness, hut most of them are epic recessive or
X-linked conditions. In any one case, only one mechanism will be operating. It
two blind people have children, their children will only be at risk the parents have
exactly the same condition causing the blindness. Or if a dominant allele affects
one of them.

GENETIC DISEASES
A single new mutation can give rise to a dominant autosomal disease and
sex-linked disorders. Recessive disorders, however, cannot be explained so simply
because both parents must carry the same aberration for the condition to occur.
Rate recessive diseases may be explained by the lack of selection against a
mutation which causes the heterozygote on ill-effects, thus allowing the mutation
to remain until, eventually, two people carrying the same mutation meet and
produce a child who then suffers from the particular disease. There are, however,
a number of relatively common recessive autosomal diseases (e.g. sickle-cell
anaemia; cystic fibrosis) for which explanations of their high frequency of
occurrence must be found. In general terms, such high frequencies are thought to
be explained by the existence of some selective advantage has been determined.
For example, in the case of sickle-cell anemia (in which the mutation occurs in the
gene for one of the components of the gas transport protein hemoglobin), whilst
thoses people who suffer from this disease (homozygous mutants) often die
prematurely, those who carry one normal allete and one mutant (stickle-cell) allete
show an increased resistance to malaria compared to people carrying two copies
of the normal allele is selected for and achieves a high frequency. In other case,
the precise nature of the advantage remaine to be elucidated-it could be that
carriers have some advantage in sexual competition, or that gametes carrying,
such alleles are somehow preferred, but evidence to support these hypotheses has
yet to be produced.

EMBRYO AND FETUS

Out increasing understanding of genetic influences or- disease increases
our ability to usefully assess the genetic make-up of the embryo and fetus. As we
enter the 21st century, parental and social expectations of normal/ perfect babies
appear greater than ever before and those involved in providing care will need to
be aware f these developments in order to provide adequate accurate information
to women (and their partners).
The options available often seem complex and sometimes variable
depending on location and economics. Consequently the Department of Health
(DoH, 2000) hae commissioned a report on prenatal genetic testing with a view to
recommending good practice.
The process of screening and diagnosing genetic disorders has advanced
significantly in recent years, making it seem easier to assess fetal normality earlier
in pregnancy. Screening test usually identify particular people or specific
population at increased risk (e.g. women over 35 years, have an increased risk of
carrying a fetus affected by Downs syndrome, but not all women over 35 years
will go on to have an affected fetus. Diagnostic tests are more specific and are
applied to specific woman who following screening are considered to be at greater
risk than the general population.

GENETIC COUNSELING/ ADVICE

Women and their partners n a higher-risk category are faced with some
challenging decisions early in pregnancy, or beforehand. They will need
opportunities to seek accurate, relevant information and time to consider the
options available. This process maybe provided by specialists trained in genetic
counseling, and this may be the midwifes responsibility.
Genetic counseling is there to facilitate effective decision-making,
enabling deliberation on the internal (e.g. personal values and beliefs, previous
experiences, expectations of this or subsequent pregnancy) and external factors
(cultural values, religious beliefs, family and friend influences, economics,
education, social circumstances) which need consideration in order for people to
make a choice that is right for them. It is also important to acknowledge that
where a partner is involved, it cannot be assumed that both parties will hold
similar views and beliefs about the pregnancy, or abnormalities which may
threaten their expectations of the child.
Counselling may be conducted before a pregnancy is begun (where there
is a known or suspected family history of genetic disorders) or where a previous
pregnancy was affected by a genetic disorder, in which case it may take place
within months of that pregnancy or prior to planning the next pregnancy.
From the midwifes viewpoint, it should be noted that the majority of
woman who seek advice will be pregnant. In order to facilitate informed choices,
there should be adequate explanations of the processes, risks and benefits,
accuracy of the rests (including information on false positives/negatives),
outcomes and alternatives for any assessments offered. This should include a
focus on how far advanced the pregnancy will be before the test can be completed
and how long the results may take to become available.
The key to successfully supporting women and their partners through this
process lies in an awareness of the influence of effective communication skills,
and of personal values and beliefs on interaction is delivered in a non-directive
manner, the professionals belief system may have an effect on decision-making.
Her evidence emphasizes the importance of relationship-building and knwowing
the women and partners expectations and beliefs in order to facilitate autonomous
decision.
To be effective, counselling should enable couples to believe that they
have made tile right decision for them, which includes accepting the
consequences. It should also be acknowledged that some women might not have
considered the possibility of abnormality until discussed with tile midwife, a
circumstance which will necessitate particular sensitivity. Unfortunately, one. of
the difficulties with effective decision-making in pregnancy is the lack of time as
gestation continues especially for women who book later than average
which may mean that significant decisions will need to be made quickly.
For various reasons (e.g. limited family histories, variations observed in
severity of a disease process), it cast sometimes be difficult to provide clear
guidelines as to inheritance, significance of outcomes and the effect (s) on
individuals in any one particular counselling situations Accordingly, any
information given needs to clarify the gaps in in knowledge as well as the
advanced mode.
It is equally imperative to discuss the impact of test on the woman, and
any significant other people in her life, as previously mentioned influences might
be consequential to responsibility for and acceptance of any decisions made.
Women (and their partners) who have been thus unshelled will than have
decisions to make. The choices open to them may include:
Not becoming pregnant, and opting for fostering or adoption
Utilizing the facilities available for infertility treatments, e.g. opting for
artificial insemination by donor
Continuing with the pregnancy (if appropriate) and hoping for the best
Undergoing antenatal diagnostic tests, with the option to:
- Keep the pregnancy regardless of outcome
- Terminate the pregnancy if a positive diagnosis is made
Using the other alternatives that may be available in some cases, e.g. gene
therapy.
The choices are nearly always complex, and consequently it is crucial that
accurate knowledge is available to facilitate the best personal decisions. Case
scenarios 12.1 and 12.2 illustrate situations that may arise.

SCEREENING FOR RISK INDICATORS

The primary aim of screening for risk indicators/markers is to provide
accurate information to facilitate fully informed decisions about proceeding with
diagnostic tests to con firm or exclude a genetic disorder There are various
indicators and the utility of these in individual cases may dispread on available
information, previous history, the duration of gestation and parental expectations
of normality.

History-taking
History-talking is a significant factor in plant in planning care for the
pregnant woman. It provides detailed information and an opportunity for
relationshipbudding between the woman and the midwife, which although
always important, may be particularly relevant for further decision-making. An
accurate, detailed personal family, medical and obstetric history is essential in
identifying risk factors that expose the pregnancy to genetic disorders. This should
also include personal, faintly and medical information about the genetic father of
tile fetus, where possible. Sensitivity to the fact that information is not always
available is important, especially where there is no contact with the father or
where infertility treatment has been used to achieve the pregnancy.
Consideration of racial and/or geographical origins may also be
appropriate (e.g. TaySachs disease in Ashkenazi Jews, or haemaglobinopathies
in women of Mediterranean, African or Asiatic origin). Situations such as
consanguinity (close relatives, e.g. cousins, achieving a pregnancy) should also be
examined.
Once history-taking has been completed, the mid wife and woman/couple
should consider the need for further screening. Prior to any decisions, it is
essential that the woman is aware that further screening may ultimately lead to a
decision about keeping or terminating the pregnancy. For some women, this may
be unthinkable and they should be clearly aware of this scenario, whereas for
others having this choice would be essential. There may be some women who
choose to continue with screening anyway, with the view that they would like to
know details and prepare for the birth accordingly.

Ultrasound scanning (USS)

This is a non-invasive method of viewing the fetus. in the UK, the
majority of women have access to USS, usually between 1820 weeks gestation.
In addition to confirming the pregnancy, assessing gestational age, localizing the
placenta and monitoring fetal growth. it has a significant role to play in screening
for structural fetal abnormalities.
It is considered to be relatively safe, although various research studies
have been somewhat inconclusively controversial about its use. Neilson (2000)
reviewed nine good-quality trials up to July 1998 and confirmed that early USS
enabled better assessment of gestational age, detection of multiple pregnancy and
earlier diagnosis of clinically unsuspected fetal abnormalities. However, this
review also concluded that the benefits of other clinical outcomes were less clear.
Many units now offer USS at 11-14 weeks gestation, which may predict a
risk of chromosomal abnormality by measuring the amount of fluid behind the
neck of the fetus, specifically the nuchal fold thickness. It is measured in
millimeters, computer recorded in conjunction with maternal age, and used to
determine a predictive risk rate. Nicolaides et al (1994) reported that this method
compared favorably with screening of maternal age and serum biochemistry.

DIAGNOSTIC TEST
If an increased risk is established by any of the above procedures, the next
step may be to proceed to a diagnostic test, which should, generally, provide more
definite information about the fetal genetic women constitution.
As stated earlier, it is essential that women are aware et the hazards
attached to such procedures. These include the risks that the test may pose to the
pregnancy, the risks of false positive or negative results and the danger of being
faced with having to choose termination. These choices may be more difficult for
some women than for others, depending on their expectations, beliefs and needs
for their pregnancy, as well as multiple psychosocial influences.
The purpose of testing is to assess the status of the genome of an
individual embryo or fetus. Each individuals genome is unique (with the
exception of that of identical twins) and, in order to be able to recognize
individual sequences of DNA, techniques have been developed to provide
methods of analysis for the DNA of an individual. These techniques use genetic
probes which are labeled fragments of DNA) to determine whether a particular
DNA sequence is present or absent. Embryonic/ fetal genome analysis in only one
application of this technology, others include forensic science and paternity
disputers.
DNA can be isolated easily from any human cell that is alive and has a
nucleus, including buccal cells and skin fibroblasts. The DNA probe is a copy of a
relevant sequence that is identifiable and can be used as a probe to hybridize a
corresponding copy of the sample.

Preimplantation Genetic Diagnosis (PGD)

This is a recent option for diagnosing genetic disorders, it was reviewed in
1999/2000 by the Human Fertilisation and Embryology Authority (HFFA) in
collabroboration with the advisory Committeee on Genetic Testing
(HFEA/ACGT), 1999), to consider a number of pratical, ethical and legal issues
associated with its viability.
This technique has to be considered before conception and involves
extrauterine assessment of the embryo. It has two stages: firstly, in vitro
fertilization techniques are used to create embryos, and these are then tested for
particular genetic disorders or to establish their sex (where the disorder is sex-
linked) (HFEA/ACGT, 1999).
Currently, PGD appears to be only used tar severe/life-threatening
disorders. The HFEA (after public eon sultation in 1993) rejected the use of PGD
for sex selection, on social grounds.
 This technique is in its infancy, but deserves mention here because women
who become aware of it may request further information. Draper arid Chadwict.
1999).
Chorionic Villus sampling (CVS)
This diagnostic test is performed in conjunction with USS. It involves
placing a fine catheter/forceps intracervically or intra-abdominally Into the
chorionic tissue of the developing embryo to extract a small biopsy sample. DNA/
cytogenetic analysis and some biochemical studies can be performed on the
material recovered (DoH, 2000). CVS is now usually carried out no carlier than at
10 weeks gestation, as a report from Oxford in the early 1990, suggested a high
risk of fetal limb deformities when it is performed below this age. However,
further research by Firth et al. (1994) was inconclusive about the reasons for the
anomalies. Alfirevic (2000), who compared early amniocentesis with CVS,
suggested an increased risk of heamangioma with CVS. Several studies also
report higher associated miscarriages (1-3%; DoH, 2000), although this can be
difficult to assess because of the increased risk of spontaneous miscarriage carlier
in pregnancy. This may be an acceptable risk for some woman who will balance
this opportunity with the need to have results to allow them to make an earlier
decision.

Amniocentesis
Amniocentesis involves sampling the amniotic fluid and the cells within it.
The process cur-ails guiding a fine needle into the amniotic sac, using USS to
localize the placenta. The biochemical constituents of the fluid may be tested for
non-specific indicators of abnormality (e.g. AFPs), for the accumulation of
specific metabolites in suspected inborn errors of metabolism. or, in Cater
pregnancy, for fetal assessment. The cells isolated from die fluid are cultured in
the laboratory to determine the fetal karyotype, or mote detailed DNA analyses
(including fetal sexing) and/or for enzyme assays. Traditionally, amniocentesis is
carried out between 16-18 weeks gestation, when maternal age, history or
screening indicate a high risk of abnormality, but this usually means that results
are not available until more than 20 weeks of gestation have elapsed.
Amniocentesis has thus been tried at earlier stages of pregnancy, but Alfirevic
(2000) found that there appeared to be increased risks of spontaneous miscarriage
and neonatal talipes associated with earlier amniocentesis, and thus these risks
would need to he weighed against the possible benefits of earlier result. Result
may occasionally be ambiguous, and there is also a small risk or contamination by
maternal cells, or of cells failing to grow. The risk of miscarriage following
amniocentesis at 1618 weeks is commonly quoted as 0.51% (DoH, 2000),
which is greater than the risk of spontaneous miscarriage at this stage of
pregnancy.

Fetoscopy
This is the technique of observing the fetus through a fine fibreoptic
telescope, during which samples of tissue may be removed, under direct vision,
for analysis. It may be used to diagnose skin disease such as epidermolysis bullosa
lethalis by skin biopsy. It is also possible to use it to perform therapeutic
intervention, e.g. blood transfusion in rhesus incompatibility.

Cordocentesis
This, technique is used to obtam a sample of fetal blood. The sample can
be used to screen for chromosomal abnormalities, haemophilia and
haemoglobinopahies. It is curried out using USS to to guide a fine needle to the
base of the umbilical cord, where a sample of fetal blood is extracted for analysis
and/ or karyothyping. It is usually carried out after 16 weeks gestation and caries
some risks, e.g. bleeding from the cord may compromise fetal well-being.
All screening and diagnostic test carry some risks, psychological and/ or
physical; consequently the decision to proceed or not needs to be carefully
measured, and the role of the midwife is in trying to ensure that couples are given
the opportunity to make fully informed decisions which they are then resolved to
make responsibility for.
GENETIC ENGINEERING
Research in genetics, at the molecular level in particular (described by
several different terms, such as the new genetics, recombinant DNA technology,
gene manipulation, genetic englearing is an especially active arena of stentific
endeavour at the moment.
It was in the early 1970s that scientists firs discovered procedures by
which they colud directly alter the genetic constitution of bacteria- the
experimental organisms first used in this kind of work (Nicholl, 2002). It was
found that, by constructing novel DNA molecules h.e. that were not found
naturally recombinant DNA molecules) in the laboratory using DNA originally
isolated from different species (e.g. a bacterium and a mammal), genes from other
organisms could be stabely introduced into a bacterial cell. Moreover, bacterial
cells containing such molecules could then produce proteins encoded by these
genes that they would not normally synthesize (e.g. mammalian proteins).