Reproductive Sequencing

REPROSEQUENCING-NGS
Every parent hopes to have a healthy child. The good news is most
babies are born healthy. However, some families planning to have
children may be faced with the diagnosis of a genetic disease. NGS
has major roles in current Medicine likes
preconception,preimplantation,prenatel and postnatal genetics
diseases, these are the approaches have been followed to avoid an
abnormal baby birth and deliver a good healthy baby. The Updating
technology of Next Generation Sequencing recently been much role
in preimplantation genetics diagnosis and etc, likes trisomy
(full/partial) or monosomy (full/partial) for chromosomes 13,
15, 16, 18, 21, or 22; triploid , segmental loss & gains
,mosaicisms and abnormalities of the sex chromosomes. It is
100% accuracy in diagnosis of above aneuploidy in IVF
division than aCGH.1

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Humans normally have 46 chromosomes in each cell, divided
into 23 pairs. Two copies of chromosome 46, one copy
inherited from each parent, form one of the pairs. X
chromosomes has more than 150 millions base pairs with 1400
genes and Y chromosomes has 50millions base pairs with 200
genes ( 46XY). Sexual region of Y is responsible for testis
determination. Nearly 30000 genes rolling for genes expression
in a human being.
FISH
Normal Male Whole Genome Sequence

Normal Female Whole Genome Sequence
3
Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two
copies of chromosome 46, one copy inherited from each parent, form one of the
pairs. X chromosomes has more than 150 millions base pairs with 1400 genes
and other X chromosomes has an inactivated while embryogenesis( 46XX). Most
of genetics disorder from maternally an originated. Nearly 30000 genes rolling for
genes expression in a cell.
FISH

Chromosome Abnormalities In Human Pregnancies (IVF)
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Ploidy: Normal chromosomes in a cell
Euploidy: Embryo genetics normal
Anuploidy: Embryo genetics abnormal.
Ex: Trisomy, Tetrasomy, Monosomy, &
Partial Trisomy-Monosomy. Segmental
Gain & Loss. Polyploidy: Two more sets
of chromosome than normal sets.

Cell division error on Genes
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Meiosis is defined as process of producing haploid.
Gametes are eggs and sperm. Meiosis cell division occur
only in spermatogonia and Oogonia. Haploid is defined as
single sets of chromosomes (1N) &diploid (2N). Cell
division occur twice but with only one replication. Shuffling
of genetics materials from both parents produce variety and
diversity.

Chromosome:1Trisomy-WGS
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First largest auto chromosome in Humans. It has over 3000 genes for
different genes coding with 249 millions base pairs(8% of total DNA of
cell). Nearly 890 diseases and disorders are associated with chromosome
1 abnormality. These includes several cancers as well as brain
degenerative disorders such as Parkinson's disease and Alzheimer's
disease. Other conditions including glaucoma and deafness are also
associated with chromosome 1 abnormalities. Trisomy of chromosome 1 is
very rare.
Source -htt://onlinelibrary.wiley.com/doi/10.1002/yea.955/pdf-web.udles
www.ncbi.nlm.nih,gog

Chromosome:2 Trisomy-WGS
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Chromosome 2 likely contains 2500 genes with 245 million base pairs that
provide instructions for making proteins. These proteins perform a variety of
different roles in the body. Changes in the structure or number of copies of a
chromosome can also cause problems with health and development. The 1q37
deletion syndrome & Trisomy 2 found in myelodysplastic syndrome.
Translocation between 2&3. ring chromosome 2, partial trisomy 2, partial
monosomy 2 & etc.
Source: National Human Genome research institute: Chromosome
abnormalities

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Chromosome 3 spans about 200 million base pairs with 1900 genes (the
building blocks of DNA) and represents approximately 6.5 percent of the
total DNA in cells. Many genetic conditions are related to changes in
particular genes on chromosome 3.
Source: National Human Genome research institute: Chromosome
abnormalities

Chromosome:4 Tri &Monosomy-WGS
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Chromosome 4 cover about 191 million DNA building blocks (base pairs)
with 1600 genes and represents more than 6 percent of the total DNA in
cells. Wolf-Hirschhorn syndrome is caused by a deletion of gene at the end
of the short (p) arm of chromosome 4 at a position described as 4p16.3.
PDGFRA-associated chronic eosinophilic leukemia is caused by genetic
abnormalities that involve the PDGFRA gene on chromosome
4. Facioscapulohumeral muscular dystrophy is caused by genetic changes
involving the long (q) arm of chromosome 4. Mosaic trisomy 4 is very rare;
only a few cases have been reported. Trisomy 4 occurs when cells have
three copies of chromosome 4 instead of the usual two
copies. https://ghr.nlm.nih.gov/chromosome/4.

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Chromosome 5 spans about 181 million DNA building blocks (base pairs)
with 1700 genes and represents almost 6 percent of the total DNA in
cells. Deletion of a region of DNA from the long (q) arm of chromosome 5
is involved in a condition called 5q minus (5q-) syndrome or
myelodysplastic syndrome (MDS). Affected individuals also have an
increased risk of developing a fast-growing blood cancer known as acute
myeloid leukemia (AML). Cri-du-chat (cat's cry) syndrome is caused by a
deletion of the end of the short (p) arm of chromosome 5p15.3. Several
regions of chromosome 5 have been associated with the risk of
developing Crohn disease((5q31). partial trisomy 5p or 5q and partial
monosomy may causes different genetics disorder.
continue

Cri Du Chat Syndrome 5P Del
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Symptoms are includes small head, jaw, round face
,Eyes are very fare apart, folds of skin over their
eyes and small nose bridge.
The geneticist jerome legume identified cri-du-chart syndrome in
1963.He also discovered the genetics abnormality that causes down
syndrome. In 80% cri-du-chart causes, the chromosomes caring the
deletion come from father sperms rather than mother eggs. If pairs
of chromosome don’t line up correctly during metaphase in meiosis
the structure of a chromosome can be changed. When this happen
With chromosome 5.it causes cri-du chart and it is commonest
syndrome which is caused by deletion.

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and represents between 5.5 and 6 percent of the total DNA in cells.
Chromosome 6 likely contains 1,000 to 1,100 genes that provide
instructions for making proteins. These proteins perform a variety of
different roles in the body. The 6q24-related transient neonatal diabetes
mellitus, a type of diabetes that occurs in infants, is caused by the over
activity (over expression) of certain genes in a region of the long (q) arm of
chromosome 6 called 6q24. Many genetic conditions are related to
changes in particular genes on chromosome 6.

Chromosome:7 Trisomy & 12th Mosaicism
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and represents more than 5 percent of the total DNA in cells.
Chromosome 7 likely contains 900 to 1,000 genes that provide
instructions for making proteins. These proteins perform a variety of
different roles in the body. Changes in the number or structure of
chromosome 7 occur frequently in human cancers. People inherit both
copies of chromosome 7 from their mother instead of one copy from each
parent. This phenomenon is called maternal uniparental disomy
(UPD). Williams syndrome is caused by the deletion of genetic material
from the long (q) arm of chromosome 7. Russell-Silver syndrome.
continue

Williams Syndrome 7q del
WS: is an autosomal dominant disorder caused by a deletion of about 26
genes from q arm of 7th chromosome. It is estimated about 1:7500-10000.
Sign: developmental delay & highly verbal and social, tend to love music,
mild to moderate mental retardation. Neonatal hypercalcimia and most of
systems mildly disorder.
15

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Chromosome 8 spans more than 146 million DNA building blocks (base
pairs) contains about 700 genes and represents between 4.5 and 5
percent of the total DNA in cells. Translocations of genetic material
between chromosome 8 and other chromosomes can cause 8p11 myelo-
proliferative syndrome. The most common translocation involved in this
condition, written as t(8;13)(p11;q12), fuses part of the FGFR1 gene on
chromosome 8 with part of the ZMYM2 gene on chromosome 13. The
translocations are found only in cancer cells. Trisomy 8 occurs when cells
have three copies of chromosome 8 instead of the usual two
copies. Langer-Giedion syndrome and recombinant 8 syndrome.

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Chromosome 9 is made up of about 141 million DNA building blocks (base
pairs) contains 800 to 900 genes and represents approximately 4.5 percent
of the total DNA in cells. The Philadelphia chromosome has been identified in
most cases of a slowly progressing form of blood cancer called chronic
myeloid leukemia (CML). (partial trisomy &partial monosomy are not
common. The 9q22.3 micro deletion, bladder cancer kleefstra syndrome are
most offend disorder.

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pairs) contains 700 to 800 genes and represents between 4 and 4.5
percent of the total DNA in cells. Changes in the number and structure of
chromosome 10 are associated with several types of cancer. Variations in
a particular region of chromosome 10 have been associated with the risk
of developing Crohn disease(10q21.1). A complex rearrangement
(translocation) of genetic material between chromosomes 10 and 11 is
associated with several types of blood cancer known as leukemia (MLL
gene).

Chromosome:11 Monosomy-WGS
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contains 1,300 to 1,400 genes and represents between 4 and 4.5 percent
of the total DNA in cells. Beckwith-Wiedemann syndrome results from the
abnormal regulation of genes on part of the short (p) arm of chromosome
11. The genes are located close together in a region designated 11p15.5
near one end of the chromosome. Emanuel syndrome is caused by the
presence of extra genetic material from chromosome 11 and chromosome
22 in each cell. WAGR syndrome (11p13 del). Russell-Silver syndrome
(11p15.5 region). Potocki-Shaffer syndrome (11p11.2). Jacobsen
syndrome (11q terminal deletion disorder) are common.

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Chromosome 12 spans almost 134 million DNA building blocks (base
pairs) contains 1,100 to 1,200 genes and represents between 4 and 4.5
percent of the total DNA in cells. Changes in chromosome 12 have been
identified in several types of cancer. Pallister-Killian mosaic syndrome is
usually caused by the presence of an abnormal extra chromosome called
an iso-chromosome 12p or I (12p). Translocations involving chromosome
12 are involved in a type of blood cell cancer called PDGFRB-associated
chronic eosinophilic leukemia. Several different changes involving
chromosome 12 have been reported.

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Chromosome 13 is made up of about 115 million DNA building blocks (base
pairs) contains 300 to 400 genes and represents between 3.5 and 4 percent of
the total DNA in cells. The most of the abnormality have been observed in the
8p11myeloproliferative syndrome,retinoplastoma and trisomy 13.
Patau syndrome
Fusion of the eyes or a small or absent
eye-Cleft lip and palate
Extra fingers and toes
Mental retardation

Chromosome:14 & 16,18,20&21Trisomy
22
pairs) contains 800 to 900 genes and represents about 3.5 percent of the
total DNA in cells. Rearrangements (translocations) of genetic material
between chromosome 14 and other chromosomes have been associated
with several types of cancer. The FOXGI syndrome and ring chromosome
14 were observed.

Chromosomal Translocations - Translocations
In a reciprocal translocation
two broken off chromosome
pieces of non-homologous
chromosomes are exchanged.
This is a relatively frequent
anomaly. One finds it with an
incidence of 1:500 newborns.
Reciprocal translocations are
frequently balanced because the
entire genetic material is
present. Problems occur,
though, in gamete formation.
Another frequently observed anomaly
(1:1'000 newborns) is the robertsonian
translocation, which occurs between two
acrocentric chromosomes of groups G
and D. It is also referred to as the centric
fusion of two acrocentric chromosomes.
It is a special kind of translocation in that
on the acrocentric chromosomes (most
often chromosomes 14 and 21 or 22) the
very short, satellite-bearing arm is lost and
a centric fusion t(14q21q or 14q22q) of the
two remainder chromosomes, i.e., the long
arms of the two pieces, results.

Chromosome:15 ,5& 22Trisomy-WGS
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pairs) contains 600 to 700 genes and represents more than 3 percent of the
total DNA in cells. The chromosomal changes are observed in the 15q13.3
&15q24microdeletion,acute promylocytic leukemia,angelman syndrome &
Prader-willi syndrome.Sensorineural deafness and male infertility.

Chromosome:16& 22 Trisomy-16-22Monosomy
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pairs) contains 800 to 900 genes and represents almost 3 percent of the
total DNA in cells. Alveolar capillary dysplasia with misalignment of
pulmonary veins (ACD/MPV) is a disorder that affects the development of
blood vessels in the lungs (16q24.1).Rubinstein-Taybi syndrome. Trisomy
16 occurs when cells have three copies of chromosome 16 instead of the
usual two copies. The 16p11.2 deletion and duplication are observed.

Clinical details of 16th chromosomes
26

27
contains 1,200 to 1,300 genes and represents between 2.5 and 3 percent of
the total DNA in cells. Changes in chromosome 17 have been identified in
several additional types of human cancer.

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contains 200 to 300 genes and represents approximately 2.5 percent of the
total DNA in cell. Partial Trisomy & Monosomy of chromosome 18p (18p-q) &
deletion and translocation are analyzed in different population.
Edward Syndrome.
Severe physical and mental disabilities/Development stops at the 6 month
level/Oddly clenched fists-Liver and heart problems
Low-set ears-Small mouth/Unusual or absent fingerprints

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Chromosome 19 spans about 59 million base pairs (the building blocks of DNA)
contains about 1,500 genes and represents almost 2 percent of the total DNA
in cell.
Source: National Human Genome Research Institute &Chromosomal
Abnormalities.

Chromosome:20&21 Trisomy-WGS
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contains 500 to 600 genes and represents approximately 2 percent of the total
DNA in cell. Changes in chromosome 20 have been identified in several types
of cancer. Ring chromosome 20 & alagille are related disorder.

31
Chromosome 21 is the smallest human chromosome, spanning about 48 million
base pairs (the building blocks of DNA) contains 200 to 300 genes and
representing 1.5 to 2 percent of the total DNA in cells. A genetic rearrangement
(translocation) involving chromosome 21 is associated with a type of blood
cancer known as core binding factor acute myeloid leukemia (CBF-AML).The
feature of down syndrome.
continue

Chromosome:21& 22 Trisomy-WGS
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Chromosome 22 is the second smallest human chromosome, spanning more
than 51 million DNA building blocks (base pairs) contains 500 to 600 genes and
representing between 1.5 and 2 percent of the total DNA in cells. Several types
of blood cancer known as leukemia are associated with a translocation of
genetic material between chromosomes 9 and 22. The Philadelphia
chromosome has been identified in most cases of a slowly progressing form of
blood cancer called chronic myeloid leukemia (CML). The 22q11.2 deletion
syndrome,22q11.2 duplication,22q13.3 deletion syndrome, dermato-
fibrosarcoma pro-tuberans, Emanuel syndrome, Ewing sarcoma and Optiz
G/BBB syndrome have observed commonly.

12th Chromosome Mosaicism-WGS
34
The extra copy is due to an intra chromosomal
duplication or an extra copy on a derivative
chromosome. Patients with tetrasomy 12p, or
Pallister-Killian syndrome (PKS), additionally
present with sparse temporal hair, eyebrows,
and eyelashes, prominent forehead, a cupid-
bow shaped mouth, and large ears. Only about
24 cases with mosaicism for a structural
abnormality of an auto some have been
reported in the literature.

Segmental Loss(4th) & Gain(7th)-WGS
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Wolf-Hirschhorn syndrome is caused by a deletion of genetic material near
the end of the short (p) arm of chromosome 4 at a position described as
4p16.3-A specific translocation involving chr4&14 t(4;14)(p16;q32), is found
in multiple myeloma(bone cancer). Greig cephalopolysyndactyly syndrome
results from a rearrangement (translocation) of genetic material between
chromosome 7 and another chromosome.

Segmental Loss(18q) &Gain(16p)-WGS
36
The 18q deletion syndrome is caused by a deletion of genetic material from the
long (q) arm of chromosome 18. This chromosomal change is written as 18q-.
The signs and symptoms of 18q deletion syndrome are probably related to the
loss of multiple genes in this region. Two types are distal 18q deletion syndrome
& proximal 18q deletion syndrome with different clinical features. A 16p11.2
duplication is an extra copy of the same 600 kb segment of chromosome 16 that
is missing in 16p11.2 deletion syndrome . The 600 kb region contains more
than 25 genes, and in many cases little is known about their function.

Segmental Gain(13p&19thp)-WGS
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Translocation of genetic material involving chromosome 13 has been identified in
most people with a rare blood cancer called 8p11 myelo-proliferative
syndrome(myelo-proliferative disorder) and the development of lymphoma, a
blood-related cancer that causes tumor formation in the lymph
nodes( t(8;13)(p11;q12). The 19th chromosomes losses might have different
clinical disorder.

Deletion (18q del)-WGS
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The 8q deletion syndrome is caused by a deletion of genetic material from
the long (q) arm of chromosome 18. The18q deletion syndrome is often
categorized into two types: individuals with deletions near the end of the
long arm of chromosome 18 are said to have distal 18q deletion syndrome,
and those with deletions in the part of the long arm near the center of
chromosome 18 are said to have proximal 18q deletion syndrome. The
sign and symptoms of both deletion: hearing loss and heart abnormalities
are more common in people with distal 18q deletion syndrome, while
seizures occur more often in people with proximal 18q deletion syndrome.

Deletion (3p gain-del- +9p-9q)-WGS
39
The 9q22.3 micro-deletion is a chromosomal change in which a small piece of
the long (q) arm of chromosome 9 is deleted in each cell. Affected individuals
are missing at least 352,000 base pairs, also written as 352 kb, in the q22.3
region of chromosome ,the largest reported deletion included 20.5 million base
pairs (20.5 Mb).

Deletion 7th q & 8th q del-WGS
40
Williams syndrome is caused by the deletion of genetic material from a
portion of the long (q) arm of chromosome 7. The deleted region, which is
located at position 11.23 (written as 7q11.23), is designated the Williams-
Beuren region. This region includes 26 to 28 genes, and researchers believe
that the characteristic features of Williams syndrome are probably related to
the loss of several of these genes. Langer-Giedion syndrome is caused by a
deletion or mutation in several genes on the long (q) arm of chromosome 8
at a position described as 8q24.1.The signs and symptoms of this condition
are related to the deletion or mutation in at least two genes from this part of
the chromosome.

Sex Chromosomal Abnormality
41

Sex Chromosome:45 X Turner Syndrome-WGS
42
continue

Turner Syndrome 45x
 Sex chromosomal abnormality
 Delayed puberty
 99% are not born
 Infertility if born a female baby
 X is depart because of Mosaicism
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Klinefelter Syndrome 46+XXY-Male
 Sex-chromosome disorder in Male
 Sexually oriented system underdeveloped
(Small testes, sparse facial and pubic hair)
 Long arms and legs and big feet and hands
 May develop breast tissue
 Often infertile
 A male with Klinefelter has one extra copy of
the X chromosome (XXY), but is fully male
because of the presence of the Y
chromosome.
44

Triplo-X (46+XXX) Female
Tall stature
Menstrual abnormalities
All but 1 X is inactivated
45

46
Causes: Females XXX syndrome have an extra X chromosome. This
condition is not usually inherited. This mistake in egg or sperm cell
division is called nondisjunction.Triple x is also known as trisomy X or
Triplo-X.
Symptoms: Tall, low weight compared to height, mental retardation
ovarian failure, menstrual irregularities and increased width between eyes.
Complications a girl can sometime face with having this condition is
mental or developmental challenges. This could later lead to academic
disabilities, trouble socializing and stress and infertilities.
The extra chromosome cant eliminate but if you are expose to good
environment it can good life. 1.every 1000 newborn females suffer from
XXX syndrome. It is not specific to any one ethnic group or race. Since
many girl with XXX syndrome are healthy and have normal life.
Mother can go to genetics tests when they are pregnant

46+XXYY Syndrome (Male)
 Slightly delayed childhood development
 Behavioral problems
 ADD, OCD, and learning disabilities
 Leg ulcers due to poor circulation
 Sexual development is delayed
 Testes do not descend
 Infertile
 Abnormal (YY) sperm & abnormal (XX) egg
48

Jacobs Syndrome 46+XYY
 Sex-chromosome abnormality-Male
 1/1000 males has an extra Y
 96% of XYY males are normal
 Tall height and acne
 Criminals with chromosomal abnormalities tend to have XYY
49

Reproductive Sequencing

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