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A Patient Counseling Guide
for Reproductive Genetics
Educational content provided by
Table of contents
Genetics overview
3
Chromosome conditions
12
Single gene inheritance
37
IVF and embryo development
44
Preimplantation genetic screening (PGS)
51
Preimplantation genetic diagnosis (PGD)
54
Prenatal screening and diagnostic options
57
This Counseling Guide is intended to offer health care providers basic information on genetic counseling and is for general educational purposes only.
The guide is not intended to be used to substitute for the exercise of the health care provider’s professional judgment in providing professional services.
2
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Genetics overview
3
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Cells, chromosomes, and DNA
Human
Nucleus
DNA
Base
pairs
Cell
A
T
G
C
Chromosome
US National Library of Medicine. Help Me Understand Genetics: Cells and DNA. https://ghr.nlm.nih.gov/primer/basics.pdf. Published May 30,
2016. Accessed June 6, 2016.
4
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Cells, chromosomes, and DNA
■
The human body is made up of trillions of cells.
■
Inside the nucleus of cells, are structures called
chromosomes. Chromosomes are made up of genes.
■
Genes are individual instructions that tell the body how to
develop and function.
■
The four bases of DNA (A,T,G,C) are the building blocks of
genes. The order of these bases determines how genes
instruct our bodies.
Human
Nucleus
DNA
Base
pairs
US National Library of Medicine. Help Me Understand Genetics: Cells and
DNA. https://ghr.nlm.nih.gov/primer/basics.pdf. Published May 30, 2016.
Accessed June 6, 2016.
Cell
A
T
G
C
Chromosome
5
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening 5
and diagnostic
options
Human chromosomes
From Mother
From Father
1
2
3
6
7
8
13
14
15
9
4
5
10
11
12
16
17
18
or
19
20
21
22
Autosomes
X X
Female
X Y
Male
23
Sex Chromosomes
Image adapted from Gardner RJM, Sutherland GR, Schaffer LG. Chromosome Abnormalities and Genetic Counseling. 4th ed. New York, NY:
Oxford University Press; 2012.
6
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Human chromosomes
■Humans
typically have 23 pairs of chromosomes (for a total
of 46 chromosomes).
–Half of the chromosomes come from the mother and
the other half from the father.
■The
first 22 pairs are the same whether you are male or
female. These are called autosomes.
■The
last pair of chromosomes are called sex
chromosomes. Females typically have two copies of the
X chromosome and males typically have one X and one
Y chromosome.
From Mother
From Father
1
2
3
6
7
8
13
14
15
9
4
5
10
11
12
16
17
18
or
19
Gardner RJM, Sutherland GR, Schaffer LG. Chromosome Abnormalities and
Genetic Counseling. 4th ed. New York, NY: Oxford University Press; 2012.
20
21
22
Autosomes
X X
Female
X Y
Male
23
Sex Chromosomes
7
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening 7
and diagnostic
options
Cell division in primary germ cells (meiosis)
Primary germ cell
Chromosomes copied
1st Meiosis
2nd Meiosis
Gametes (sperm/egg)
8
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Cell division in primary germ cells (meiosis)
■The
human gametes are sperm and eggs.
■Each
gamete typically has only one set of chromosomes
(23 total).
■At
fertilization/conception, the father’s sperm joins with the
mother’s egg to form a zygote, which becomes an embryo
(with 46 chromosomes).
Primary germ cell
Chromosomes copied
1st Meiosis
2nd Meiosis
Gardner RJM, Sutherland GR, Schaffer LG. Chromosome Abnormalities and
Genetic Counseling. 4th ed. New York, NY: Oxford University Press; 2012.
Gametes (sperm/egg)
9
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening 9
and diagnostic
options
Nondisjunction – an error in cell division
Nondisjunction
Typical meiosis
Eggs
Sperm
Fertilization
Trisomy
Monosomy
10
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Nondisjunction – an error in cell division
■Aneuploidy:
an incorrect number of chromosomes
–Trisomy: three copies of a specific chromosome
–Monosomy: one copy of a specific chromosome
■Aneuploidy
can lead to:
–Failure of an embryo to implant in the uterus
–Pregnancy loss/miscarriage
–Birth of a baby with a chromosome condition
(eg., trisomy 21, which is also known as
Down syndrome)
Nondisjunction
Typical meiosis
Eggs
Sperm
Fertilization
Gardner RJM, Sutherland GR, Schaffer LG. Chromosome Abnormalities and
Genetic Counseling. 4th ed. New York, NY: Oxford University Press; 2012.
Trisomy
Monosomy
11
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening11
and diagnostic
options
Chromosome conditions
12
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Trisomy 21 (Down syndrome)
1
2
3
6
7
8
13
14
15
19
20
9
21
4
5
10
11
12
16
17
18
X X
22
13
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Trisomy 21 (Down syndrome)
■Trisomy
21 is the most common chromosome condition in
live births.
■Trisomy
21 occurs in approximately 1 in every 660 live births.
■Common
characteristics of trisomy 21:
–Intellectual disability
–Heart problems
–Low or poor muscle tone
–Characteristic facial features
Jones KL, Jones MC, del Campo M. Smith’s Recognizable Patterns of
Human Malformation. 7th ed. Philadelphia: Elsevier Saunders; 2013.
1
2
3
6
7
8
13
14
15
19
20
9
21
4
5
10
11
12
16
17
18
22
X X
14
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening14
and diagnostic
options
Trisomy 18 (Edwards syndrome)
1
2
3
6
7
8
13
14
15
19
20
9
21
4
5
10
11
12
16
17
18
X Y
22
15
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Trisomy 18 (Edwards syndrome)
■Trisomy
18 occurs in approximately 1 in every 3,333 live births.
■Severe
chromosome condition; life expectancy usually less
than 1 year.
■Common
characteristics of trisomy 18:
– Intrauterine growth retardation
– Unusual positioning of the hands and/or feet
– Severe developmental and intellectual disabilities
Jones KL, Jones MC, del Campo M. Smith’s Recognizable Patterns of
Human Malformation. 7th ed. Philadelphia: Elsevier Saunders; 2013.
1
2
3
6
7
8
13
14
15
19
20
9
21
4
5
10
11
12
16
17
18
22
X Y
16
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening16
and diagnostic
options
Trisomy 13 (Patau syndrome)
1
2
3
6
7
8
13
14
15
19
9
20
21
4
5
10
11
12
16
17
18
22
X X
17
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Trisomy 13 (Patau syndrome)
■Trisomy
13 occurs in approximately 1 in every 5,000 live births.
■Severe
chromosome condition; life expectancy usually less
than 1 year.
■Common
characteristics of trisomy 13:
– Heart, brain, kidney abnormalities
– Incomplete fusion of the lip and/or palate (clefting)
– Severe developmental and intellectual disabilities
1
2
3
6
7
8
13
14
15
19
Jones KL, Jones MC, del Campo M. Smith’s Recognizable Patterns of
Human Malformation. 7th ed. Philadelphia: Elsevier Saunders; 2013.
9
20
4
5
10
11
12
16
17
18
21
22
X X
18
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening18
and diagnostic
options
Monosomy X (Turner syndrome)
1
2
3
6
7
8
13
14
15
19
9
20
21
4
5
10
11
12
16
17
18
22
X
19
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Monosomy X (Turner syndrome)
■Monosomy
X occurs in 1-1.5% of pregnancies. However,
most (~99%) of these pregnancies do not survive to term.
–Monosomy X occurs in approximately 1 in every 2,000
female live births
■Common
characteristics of monosomy X:
– Heart defects
– Shorter than average height
– Delayed puberty
– Infertility
1
2
3
6
7
8
13
14
15
Hook EB, Warburton D. Hum Genet. 2014;133(4):417-424.
Jones KL, Jones MC, del Campo M. Smith’s Recognizable Patterns of
Human Malformation. 7th ed. Philadelphia: Elsevier Saunders; 2013.
19
9
20
4
5
10
11
12
16
17
18
21
22
X
20
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening20
and diagnostic
options
47,XXX (Triple X syndrome)
1
2
3
6
7
8
13
14
15
19
9
20
21
4
5
10
11
12
16
17
18
22
X X X
21
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
47,XXX (Triple X syndrome)
■47,XXX
occurs in approximately 1 in every 1,000 female
live births.
■Many
females with 47,XXX do not have any visible
characteristics.
■Variable
characteristics of 47,XXX:
– Taller than average height
– Learning difficulties, speech, and language delays
– Delayed development of motor skills
–
Behavioral and emotional
difficulties
1
2
3
6
7
8
13
14
15
Jones KL, Jones MC, del Campo M. Smith’s Recognizable Patterns of
Human Malformation. 7th ed. Philadelphia: Elsevier Saunders; 2013.
19
9
20
4
5
10
11
12
16
17
18
21
22
X X X
22
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening22
and diagnostic
options
47,XXY (Klinefelter syndrome)
1
2
3
6
7
8
13
14
15
19
20
9
21
22
4
5
10
11
12
16
17
18
X
X
Y
23
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
47,XXY (Klinefelter syndrome)
■Klinefelter
syndrome occurs in approximately 1 in every 500
male live births.
■Many
males with 47,XXY do not have any visible
characteristics.
■Variable
characteristics of Klinefelter syndrome:
– Speech and/or learning difficulties
– Tall stature
– Small testes
– Infertility
Jones KL, Jones MC, del Campo M. Smith’s Recognizable Patterns of
Human Malformation. 7th ed. Philadelphia: Elsevier Saunders; 2013.
1
2
3
6
7
8
13
14
15
19
20
9
21
4
5
10
11
12
16
17
18
22
X
X
Y
24
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening24
and diagnostic
options
47,XYY (Jacobs syndrome)
1
2
3
6
7
8
13
14
15
19
20
9
21
4
5
10
11
12
16
17
18
X
22
Y
Y
25
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
47,XYY (Jacobs syndrome)
■47,XYY
occurs in approximately 1 in every 840 male
live births.
■Many
males with 47,XYY do not have any visible
characteristics.
■Variable
characteristics of 47,XYY:
– Delayed development of speech and language skills
– Learning disabilities
– Autism spectrum disorder
Jones KL, Jones MC, del Campo M. Smith’s Recognizable Patterns of
Human Malformation. 7th ed. Philadelphia: Elsevier Saunders; 2013.
1
2
3
6
7
8
13
14
15
19
20
9
21
4
5
10
11
12
16
17
18
22
X
Y
Y
26
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening26
and diagnostic
options
Chromosome deletions and microdeletions
Telomere
Telomere
Telomere
p arm
p arm
p arm
p arm
Centromere
Centromere
Centromere
Centromere
q arm
q arm
q arm
q arm
Telomere
Telomere
Telomere
Telomere
Normal
Deletion
Microdeletion
Normal
27
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening27
and diagnostic
options
Chromosome deletions and microdeletions
■
Deletions and mircodeletions are caused by missing pieces
of chromosome material.
– Microdeletions are smaller than deletions and cannot
be seen under a microscope.
■
Chromosome deletions and microdeletions may result in
intellectual disability, developmental disabilities, and/or birth
defects.
Telomere
Telomere
p arm
p arm
p arm
p arm
Centromere
Centromere
Centromere
Centromere
q arm
q arm
q arm
q arm
Telomere
Normal
Telomere
Telomere
Deletion
Telomere
Normal
Telomere
Microdeletion
Gardner RJM, Sutherland GR, Schaffer LG. Chromosome Abnormalities and
Genetic Counseling. 4th ed. New York, NY: Oxford University Press; 2012.
28
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening28
and diagnostic
options
Chromosome duplications and microduplications
Telomere
Telomere
Telomere
p arm
p arm
p arm
p arm
Centromere
Centromere
Centromere
Centromere
q arm
q arm
q arm
q arm
Telomere
Telomere
Telomere
Telomere
Normal
Duplication
Microduplication
Normal
29
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening29
and diagnostic
options
Chromosome duplications and microduplications
■
Duplications and mircoduplications are caused by extra
pieces of chromosome material.
– Microduplications are smaller than duplications and
cannot be seen under a microscope.
■
Chromosome duplications and microduplications may
result in intellectual disability, developmental disabilities,
and/or birth defects.
Telomere
Normal
Telomere
p arm
p arm
p arm
p arm
Centromere
Centromere
Centromere
Centromere
q arm
q arm
q arm
q arm
Telomere
Telomere
Gardner RJM, Sutherland GR, Schaffer LG. Chromosome Abnormalities and
Genetic Counseling. 4th ed. New York, NY: Oxford University Press; 2012.
Telomere
Duplication
Telomere
Normal
Telomere
Microduplication
30
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening30
and diagnostic
options
Chromosome translocation: Reciprocal
Balanced translocation
carrier parent
Non-carrier
parent
Gamete from
non-carrier
parent
Possible
gametes from
carrier parent
Fertilization
Possible
zygotes
Non-carrier
Balanced
translocation
carrier
Partial trisomy
+ partial
monosomy
Partial trisomy
+ partial
monosomy
31
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Chromosome translocation: Reciprocal
■A
reciprocal translocation is the result of two chromosomes
exchanging segments.
■Reciprocal
translocations are present in approximately 1 in
500 individuals.
■Most
individuals who carry a reciprocal translocation do not
have any visible characteristics.
■Carriers
of a reciprocal translocation may be at risk for:
–
Infertility
–
Recurrent pregnancy loss
Balanced translocation
carrier parent
–
Babies with birth defects and/or
intellectual disabilities
Non-carrier
parent
Gamete from
non-carrier
parent
Possible
gametes from
carrier parent
Fertilization
Possible
zygotes
Non-carrier
Gardner RJM, Sutherland GR, Schaffer LG. Chromosome Abnormalities and
Genetic Counseling. 4th ed. New York, NY: Oxford University Press; 2012.
Balanced
translocation
carrier
Partial trisomy
+ partial
monosomy
Partial trisomy
+ partial
monosomy
32
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening32
and diagnostic
options
Chromosome translocation: Robertsonian
Balanced translocation
carrier parent
Non-carrier
parent
Gamete from
non-carrier
parent
Possible
gametes from
carrier parent
Fertilization
Possible
zygotes
Non-carrier
Translocation
carrier
Trisomy
Monosomy
Trisomy
Monosomy
33
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Chromosome translocation: Robertsonian
■A
Robertsonian translocation happens when two certain
chromosomes (13, 14, 15, 21, 22) join together.
■Robertsonian
translocations are present in approximately
1 in every 1,000 individuals.
■Most
individuals who carry a Robertsonian translocation do
not have any visible characteristics.
■Carriers
of a Robertsonian translocation may be at risk for:
– Infertility
–
Recurrent pregnancy loss
Balanced translocation
carrier parent
–
Babies with birth defects and/or
intellectual disabilities
Non-carrier
parent
Gamete from
non-carrier
parent
Possible
gametes from
carrier parent
Fertilization
Possible
zygotes
Gardner RJM, Sutherland GR, Schaffer LG. Chromosome Abnormalities and
Genetic Counseling. 4th ed. New York, NY: Oxford University Press; 2012.
Non-carrier
Translocation
carrier
Trisomy
Monosomy
Trisomy
Monosomy
34
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening34
and diagnostic
options
Mosaicism (an error in cell division causing cells with
a genetic change)
Fertilization
Embryo
Mosaic
Somatic cell division (mitosis)
Normal cells
Cells with genetic change
Adapted from: Campbell IM, Shaw CA, Stankiewicz P, Lupski JR. Somatic mosaicism: implications for disease and transmission genetics.
Trends Genet. 2015;31(7):382-392.
35
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Mosaicism (an error in cell division causing cells with
a genetic change)
■Mosaicism
is the presence of two or more cell lines with
different genetic make-ups.
■It
is caused by an error during cell division (mitosis).
■The
proportion of each cell line is variable.
–
The clinical impact of mosaicism on an individual varies
depending on the number and type of cells affected.
Fertilization
Embryo
Somatic cell division (mitosis)
Mosaic
Normal cells
Cells with genetic change
U.S. National Library of Medicine. Medical Encyclopedia: Mosaicism. https://
www.nlm.nih.gov/medlineplus/ency/article/001317.htm
Updated May 3, 2016. Accessed June 3, 2016.
36
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening36
and diagnostic
options
Single gene inheritance
37
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Autosomal dominant inheritance
Parents
mutation
normal
Unaffected
Affected
Children
Unaffected
(50%)
Affected
(50%)
38
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Autosomal dominant inheritance
■With
autosomal dominant inheritance, only one copy of a
mutated gene is necessary for the condition to be present.
■An
affected parent has the following reproductive risks per
pregnancy:
–
50% chance to have a fetus affected with the condition
–
50% chance to have a fetus without the condition
(unaffected)
–
Males and females are at equal risk
Parents
mutation
normal
Affected
Unaffected
Children
US National Library of Medicine. Help Me Understand Genetics: Inheriting
Genetic Conditions. https://ghr.nlm.nih.gov/primer/inheritance.pdf.
Published June 6, 2016. Accessed June 7, 2016.
Unaffected
(50%)
Affected
(50%)
39
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening39
and diagnostic
options
Autosomal recessive inheritance
Parents
mutation
mutation
normal
normal
Carrier
Carrier
Children
Unaffected
non-carrier (25%)
Carrier
(50%)
Affected
(25%)
40
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Autosomal recessive inheritance
■With
autosomal recessive inheritance, two copies of a
mutated gene are necessary for the condition to be present.
■Individuals
with only one copy of a mutated gene are called
carriers and are typically unaffected.
■If
both parents are carriers of the same condition, they
have the following reproductive risks per pregnancy:
–
25% chance to have a fetus affected with the condition
–
50% chance to have a fetus who is a carrier of the condition
–
25% chance to have a fetus
without the condition and a
non-carrier (unaffected noncarrier)
–
Males and females are at equal
risk
US National Library of Medicine. Help Me Understand Genetics: Inheriting
Genetic Conditions. https://ghr.nlm.nih.gov/primer/inheritance.pdf.
Published June 6, 2016. Accessed June 7, 2016.
Parents
mutation
mutation
normal
normal
Carrier
Carrier
Children
Affected
(25%)
Carrier
(50%)
Unaffected
non-carrier (25%)
41
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening41
and diagnostic
options
X-linked recessive inheritance
Parents
mutation
X
X
Y
X
normal
Carrier
Unaffected
Children
X
Y
X
Unaffected
(25%)
X
X
Unaffected non-carrier
(25%)
X
X
Carrier
(25%)
Y
Affected
(25%)
42
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
X-linked recessive inheritance
■X-linked
inheritance involves a mutated gene that occurs on the
X chromosome.
■Males who have a mutated gene on their X chromosome are affected
with the condition.
■Females who have a mutated gene on one of their two
X chromosomes are called carriers of the condition.
–
Female carriers are typically unaffected; however, some female carriers
may display characteristics of the condition.
■Females
who carry an X-linked recessive condition have the following
reproductive risks per pregnancy:
–
25% chance of having a son who is not affected with the condition
–
25% chance of having a daughter
who is not a carrier of the condition
–
25% chance of having a daughter
who is a carrier of the condition
–
25% chance of having a son who
is affected with the condition
Parents
mutation
X
X
Y
X
normal
Carrier
Unaffected
Children
US National Library of Medicine. Your guide to understanding genetic
conditions: What are the different ways in which a genetic condition can be
inherited? https://ghr.nlm.nih.gov/primer/inheritance/inheritancepatterns.
Published May 31, 2016. Accessed June 3, 2016.
X
Y
X
Unaffected
(25%)
X
X
X
X
Unaffected non-carrier
(25%)
Carrier
(25%)
Y
Affected
(25%)
43
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening43
and diagnostic
options
IVF and embryo development
44
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
In vitro fertilization (IVF)
Uterus
Ovary
1
3
Ovarian stimulation
and egg retrieval
Embryo transfer
2
Fertilization
45
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
In vitro fertilization (IVF)
■There
are 3 main steps in an IVF cycle:
1. Ovarian stimulation and egg retrieval
2. Fertilization – sperm and egg are combined in the laboratory
to form an embryo
3. Embryo transfer into the uterus or frozen for future use
Uterus
Ovary
1
3
Ovarian stimulation
and egg retrieval
Embryo transfer
2
Fertilization
46
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening46
and diagnostic
options
Percentage of embryos with a chromosome
abnormality (aneuploidy) increases with maternal age
% of Embryos With Aneuploidy
90
80
70
60
50
40
30
20
10
0
<35
35-37
38-40
41-42
>42
Maternal Age
Harton GL, et al. Fertil Steril. 2013;100(6):1695-1703.
Harton GL, et al. Fertil Steril. 2013;100(6):1695-1703.
47
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Percentage of embryos with a chromosome
abnormality (aneuploidy) increases with maternal age
■Aneuploid
embryos can occur in women of all ages, but
the risk increases with maternal age.
■Risks
associated with an aneuploid embryo:
– Implantation failure
–
Miscarriage
–
Babies born with birth defects/intellectual disabilities
% of Embryos With Aneuploidy
90
80
70
60
50
40
30
20
10
0
<35
35-37
38-40
41-42
>42
Maternal Age
Harton GL, et al. Fertil Steril. 2013;100(6):1695-1703.
Scott RT Jr., et al. Fertil Steril. 2012;97(4):870-875.
Harton GL, et al. Fertil Steril. 2013;100(6):1695-1703.
48
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening48
and diagnostic
options
Stages of embryo development
2-cell stage
8-cell stage
(cleavage stage)
Blastocyst
(100+ cells)
Inner cell mass
Fertilization
Day 2
Day 3
Outer layer
(Trophectoderm)
Day 5
49
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Stages of embryo development
■Following
■Cell
egg retrieval, fertilization occurs in the laboratory.
division occurs in the days following fertilization.
■By
day 5, a blastocyst has formed with an outer layer and
an inner cell mass.
2-cell stage
8-cell stage
(cleavage stage)
Inner cell mass
Fertilization
Day 2
Day 3
Blastocyst
(100+ cells)
Outer layer
(Trophectoderm)
Day 5
Harton GL, et al. Fertil Steril. 2013;100(6):1695-1703.
50
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening50
and diagnostic
options
Preimplantation genetic screening
(PGS)
51
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Preimplantation genetic screening (PGS)
Embryo unlikely to
have aneuploidy
Embryo likely to
have aneuploidy
1
2
3
Embryo Biopsy
Chromosome Screening
Embryo Transfer
52
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Preimplantation genetic screening (PGS)
■PGS
process:
1.Embryo Biopsy: One or more cells from each embryo is
removed for screening
2.Chromosome Screening: Biopsied cells are screened for
aneuploidy (too many or too few chromosomes)
3.Embryo Transfer: Embryos that are unlikely to have
aneuploidy are available for transfer into the uterus or can be
frozen for future use
■Potential
benefits:
–
Increased implantation, pregnancy, and live birth rates
–
Decreased miscarriage rates
–
Selection of most viable embryo
for single embryo transfer
■Limitations:
Embryo unlikely to
have aneuploidy
–
PGS only screens for aneuploidy
–
PGS does not screen for other
conditions
–
PGS is not 100% accurate
Forman EJ, et al. Fertil Steril. 2013;100(1):100-107.
Scott RT Jr, et al. Fertil Steril. 2013;100(3):697- 703.
Harton GL, et al. Fertil Steril. 2013;100(6):1695-1703.
Dahdouh EM, et al. J Obstet Gynaecol Can. 2015;37(5):451-63.
Embryo likely to
have aneuploidy
1
2
3
Embryo Biopsy
Chromosome Screening
Embryo Transfer
53
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening53
and diagnostic
options
Preimplantation genetic diagnosis
(PGD)
54
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Preimplantation genetic diagnosis (PGD)
Embryo likely to be unaffected
Embryo likely to be affected
1
2
3
Embryo Biopsy
Genetic Testing
Embryo Transfer
55
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Preimplantation genetic diagnosis (PGD)
■PGD
process:
1.Embryo Biopsy: One or more cells from each embryo is
removed for testing
2.Genetic Testing: Biopsied cells are tested for the inherited
condition of interest
3.Embryo Transfer: Embryos that are likely to be unaffected
with the condition are available for transfer to the uterus or
can be frozen for future use
■Benefits:
–
Reduced risk of having a baby with an inherited condition
■Limitations:
Embryo likely to be unaffected
–
PGD does not test for all
possible conditions
–
PGD is not 100% accurate
Embryo likely to be affected
1
2
3
Embryo Biopsy
Genetic Testing
Embryo Transfer
Practice Committee of Society for Assisted Reproductive Technology;
Practice Committee of American Society for Reproductive Medicine. Fertil
Steril. 2008;90(5 Suppl):S136-143.
Dahdouh EM, et al. J Obstet Gynaecol Can. 2015;37(5):451-463.
56
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening56
and diagnostic
options
Prenatal screening and
diagnostic options
57
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Prenatal screening and diagnostic options*
NO
Patient counseled and elects
prenatal testing
YES
Serum
screening
cfDNA
screening
10 0/7 weeks - 22 6/7 weeks of pregnancy
10 weeks of pregnancy until delivery
Is the result positive
for a chromosome
condition?
Is the result positive
for a chromosome
condition?
YES
CVS/Amniocentesis
CVS: 10-13 weeks of pregnancy
Amniocentesis: typically 15-20 weeks of pregnancy
YES
Offer further counseling
and diagnostic testing
NO
NO
Patient and provider
to discuss next steps
Diagnostic
Patient and provider
to discuss next steps
Patient and provider
to discuss next steps
ACOG Practice Bulletins—Prenatal Diagnostic Testing for Genetic Disorders. Obstet Gynecol. 2016;127:e108–e122.
ACOG Practice Bulletins—Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127:e123–e137.
58
*Typical in USA but may differ by country.
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Prenatal screening and diagnostic options*
■Prenatal
aneuploidy screening assesses a woman’s risk of
carrying a fetus with certain chromosome conditions.
–If a screening result is positive, further counseling and
diagnostic testing should be offered
■Diagnostic
testing can provide definitive information about:
–
Chromosome conditions
–
Certain genetic conditions
Patient counseled and elects
prenatal testing
NO
YES
Serum
screening
cfDNA
screening
10 0/7 weeks - 22 6/7 weeks of pregnancy
10 weeks of pregnancy until delivery
Is the result positive
for a chromosome
condition?
Is the result positive
for a chromosome
condition?
YES
ACOG Practice Bulletins—Prenatal Diagnostic Testing for Genetic Disorders.
Obstet Gynecol. 2016;127:e108–e122.
ACOG Practice Bulletins—Screening for Fetal Aneuploidy. Obstet Gynecol.
2016;127:e123–e137.
NO
Patient and provider
to discuss next steps
Diagnostic
YES
Genetics
overview
Chromosome
conditions
Offer further counseling
and diagnostic testing
NO
Patient and provider
to discuss next steps
Patient and provider
to discuss next steps
59
*Typical in USA but may differ by country.
TOC
CVS/Amniocentesis
CVS: 10-13 weeks of pregnancy
Amniocentesis: typically 15-20 weeks of pregnancy
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening59
and diagnostic
options
Cell-free DNA (cfDNA) screening
Unaffected
pregnancy
Affected
pregnancy
CCCTTAGCGCTTTAACGTACGTAAAACCCTT
AACGTACGTAAAAACGGGGTCAAAGGTTCCC
GACTTAAAATCGGAATCGATGCCCAAACTT
AATCGATGCCCAAACGGGGTCAAAGTTCCC
Maternal cfDNA
Fetal cfDNA
1
3
Analysis
via counting
2
Sequencing
of cfDNA
Maternal blood draw
and isolation of cfDNA
60
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Cell-free DNA (cfDNA) screening
■cfDNA
screening process:
1.Blood is drawn from pregnant woman’s arm at 10 weeks of gestation
or greater. cfDNA is isolated from the maternal blood in the laboratory.
2.cfDNA is sequenced to determine chromosome of origin
3.Sequenced cfDNA is counted to screen for chromosome conditions
■Benefits:
–
High detection rates for conditions tested
–
Very low false positive rates
● Fewer patients will need to have follow-up diagnostic testing
compared with serum screening
■Limitations:
–
Not diagnostic (false positives
and false negatives can occur)
–
In some instances, results may
represent a maternal, rather
than fetal, condition
Unaffected
pregnancy
Affected
pregnancy
CCCTTAGCGCTTTAACGTACGTAAAACCCTT
AACGTACGTAAAAACGGGGTCAAAGGTTCCC
GACTTAAAATCGGAATCGATGCCCAAACTT
AATCGATGCCCAAACGGGGTCAAAGTTCCC
Maternal cfDNA
Fetal cfDNA
1
Gil MM, et al. Ultrasound Obstet Gynecol. 2015;45(3):249-266.
ACOG Practice Bulletins—Screening for Fetal Aneuploidy. Obstet Gynecol.
2016;127:e123–e137.
Maternal blood draw
and isolation of cfDNA
2
Sequencing
of cfDNA
3
Analysis
via counting
61
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening61
and diagnostic
options
Classification of cfDNA screening results
Negative cfDNA results
Positive cfDNA results
True
negatives
True
positives
False positives
and
false negatives
62
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Classification of cfDNA screening results
■
True
positive: a positive result, and the fetus has
the condition
■
False
positive: a positive result, but the fetus does not
have the condition
■
True
negative: a negative result, and the fetus does not
have the condition
■False
negative: a negative result, but the fetus has
the condition
Negative cfDNA results
Positive cfDNA results
True
negatives
True
positives
False positives
and
false negatives
63
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening63
and diagnostic
options
cfDNA: Negative results
Negative
cfDNA results
Fetuses who have the condition
(false negatives)
64
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
cfDNA: Negative results
■The
chance that the fetus does not have the condition is
greater than 99%.
–
False negatives do occur rarely
■The
results apply only to the conditions tested.
■No
additional screening tests for aneuploidy should be offered
as this will increase the potential for a false positive result.
Negative
cfDNA results
ACOG Practice Bulletins—Screening for Fetal Aneuploidy. Obstet Gynecol.
2016;127:e123–e137.
Gil MM, et al. Ultrasound Obstet Gynecol. 2015;45(3):249-266.
Fetuses who have the condition
(false negatives)
65
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening65
and diagnostic
options
cfDNA: Positive results
No additional risk factors present
Additional risk factor(s) present
All positive cfDNA results
Fetuses who have
the condition
66
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
cfDNA: Positive results
■A
positive result means the fetus has an increased chance
of having a chromosome condition.
■The
overall chance for the condition depends on a
combination of the cfDNA result and any additional risk
factors, including:
–
Maternal age
–
Ultrasound results
–
Serum screening results
–
Family history of chromosome condition
■Further
counseling and
diagnostic testing should
be offered.
No additional risk factors present
Additional risk factor(s) present
All positive cfDNA results
Fetuses who have
the condition
ACOG Practice Bulletins—Screening for Fetal Aneuploidy. Obstet Gynecol.
2016;127:e123–e137.
67
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening67
and diagnostic
options
Diagnostic testing: chorionic villus sampling (CVS)
Placenta
Ultrasound probe
Placenta
Chorionic
villi
Ultrasound probe
Chorionic villi
Transcervical CVS
Transabdominal CVS
68
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Diagnostic testing: chorionic villus sampling (CVS)
■Can
determine, with as much certainty as is possible,
whether a chromosome condition is present.
–
Additional genetic testing can be performed if indicated
■Involves
testing of cells collected from the placenta.
–
Typically performed between 10 weeks and 13 weeks
of pregnancy
■Has
a risk of miscarriage.
Placenta
Ultrasound probe
Placenta
Ultrasound probe
Chorionic
villi
Chorionic villi
Transcervical CVS
Transabdominal CVS
ACOG Practice Bulletins—Prenatal Diagnostic Testing for Genetic Disorders.
Obstet Gynecol. 2016;127:e108–e122.
69
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening69
and diagnostic
options
Diagnostic testing: Amniocentesis
Ultrasound probe
Amniotic fluid
Uterine wall
70
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Diagnostic testing: Amniocentesis
■Can
determine, with as much certainty as is possible,
whether a chromosome condition is present.
–
Additional genetic testing can be performed if indicated
■Involves
testing of fetal cells collected from fluid
surrounding the fetus (amniotic fluid).
–
Typically performed between 15 weeks and 20 weeks of
pregnancy
■Has
a risk of miscarriage.
Ultrasound probe
Amniotic fluid
Uterine wall
ACOG Practice Bulletins—Prenatal Diagnostic Testing for Genetic Disorders.
Obstet Gynecol. 2016;127:e108–e122.
71
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening71
and diagnostic
options
Types of fetal chromosomal mosaicism
Normal cells
Chromosomally
abnormal cells
Generalized
mosaicism
Fetal
mosaicism
Confined placental
mosaicism
Kalousek DK. Pediatr Pathol. 1990;10(1-2):69-77.
Kalousek DK. Pediatr Pathol. 1990;10(1-2):69-77.
72
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options
Types of fetal chromosomal mosaicism
■Generalized
mosaicism: presence of two or more
chromosomally different cell lines in both the placenta and
the fetus.
–
Can lead to a false positive or a false negative cfDNA result
■
Confined
placental mosaicism: presence of two or
more chromosomally different cell lines in the placenta, but
not the fetus.
–
Can lead to a false positive cfDNA result
■
Fetal
mosaicism: presence of two or more chromosomally
different cell lines that are
present in the fetus, but not the
placenta.
Normal cells
Chromosomally
abnormal cells
–
Can lead to a false negative
cfDNA result
Generalized
mosaicism
Confined placental
mosaicism
Grati FR. J Clin Med. 2014;3(3):809-837.
Van Opstal D, et al. PLoS One. 2016;11(1):e0146794.
Fetal
mosaicism
Kalousek DK. Pediatr Pathol. 1990;10(1-2):69-77.
73
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening73
and diagnostic
options
This Counseling Guide is intended to offer health care providers basic information on genetic counseling and is for
general educational purposes only. The guide is not intended to be used to substitute for the exercise of the health
care provider’s professional judgment in providing professional services.
© 2016 Illumina, Inc. All rights reserved.
TOC
Genetics
overview
Chromosome
conditions
Single gene
inheritance
IVF and embryo
development
Preimplantation
genetic screening
(PGS)
Preimplantation
genetic diagnosis
(PGD)
Prenatal screening
and diagnostic
options