Each person is made in God’s image

(Gen. 1:27).

50% of spontaneous abortion are chromosomal abnormal Mostly triploidy. 45 XO, trisomy 16 98% of fetus with turner abort Generally 6/1000 the incidence of chromosomal

abnormalities

Unexplained infertility

Multiple abortion >2

Prior case of defective baby

Presence of congenital

anomalies

› 45% have minor single

anomalies

› 9% 3 minor anomalies

› 1.5% have major anomaly

2 or more major anomalies

may represent genetic

syndrome or chromosomal

abnormalities(10%).

`

1. Klinefelter syndrome- XXY

male in spite of having 2 X chromosomes or with a 44-XXY

chromosomes.

The Sperm containing both X and Y combines with an egg containing the X, results in a male child.

The egg may contribute the extra X chromosome.

Males with some development of breast tissue normally seen in females.

Little body hair is present, and such person are typically tall, have small testes.

Infertility results from absent sperm.

Evidence of mental retardation may or may not be present.

2. Turner syndrome –XO

have only 45 chromosomes ( 2n-1)

-externally female in spite of the presence of only one X

chromosomes which are short and flat chested like those with XXX

syndrome

3. Jacob’s Syndrome- XYY (Criminal syndrome)

XYY syndrome is an aneuploidy (abnormal number) of the sex chromosomes in which a human male receives an extra Y-chromosome

causes no unusual physical

features or medical problems.

may be slightly taller than

average

May have more severe acne

than normal.

Skeletal malformations may

also accompany

includes large hands and

feet,

have normal sexual

development and are able to

conceive children.

4. Triple-X- superfemale, metafemale, XXX

-individual has 47 chromosomes (2n +n)

affects about 1 in 1,000 females.

usually results from an error in the formation of a mother's egg cell or a father's sperm cell.

Sometimes, it occurs as a result of an error early in the embryo's development.

physically and mentally normal

May include hypertelorism, epicanthal folds, depressed nasal bridge

Delay in growth and mental development, when present, is usually mild.

Occasionally associated with Prader-Willi syndrome.

5.YO

-a condition which is lethal because x chromosome is necessary for life

Deletions (deficiencies)

Duplications

Inversions

Translocations

Deletions (deficiencies)

- Loss of a (generally small) segment of chromosome

A B C D E F G A B D E F G

C

Arise through spontaneous breakage some

chromosomes have fragile spots, radiation, UV,

chemicals, and viruses .

Ionizing radiation acts like little atomic "cannon balls",

blasting through strands of DNA or chromosomes.

Break points of chromosomes are highly reactive ("sticky"),whereas normal ends of chromosomes are capped bytelomeres, which do not readily bond to other molecules.

Why do they rejoin?

Deletion disorder in human:

1. Cri- du -chat, or cat-cry syndrome.

- Individuals with this syndrome have high pitched, plaintive cry, very similar to that of a kitten in distress.

represent a loss in chromosomal material.

Mental retardation

Slow motor skill development

Low birth weight and slow growth

Small head (microcephaly)

Partial webbing of fingers or toes

Wide-set eyes (hypertelorism)

Fragile Sites

are weak points at specific locations in chromatids

is a place where part of a chromosome attached to the rest of the chromosome. They have been identified in sex chromosomes as well as on autosomes.

EX.

2. Fragile X syndrome (FXS), Martin–Bell syndrome, or Escalante's syndrome (more commonly used in South American countries), is a genetic syndrome that is the most common known single-gene cause of autism and the most common inherited cause of intellectual disability

May arise

through unequal

crossing over

A B C D E F G

A B C D E F G

x

A B C D E F F GA B C D E G

Deletion Duplication

Changes in the numbers of genes

Cri-du-chat syndrome - Micro deletion of chromosome 5

DiGeorge syndrome - Micro deletion of chromosome 22

Schizophrenia & Obsessive Compulsive Disorder

-Micro deletion of chromosome 22 associated

Angelman syndrome- Micro deletion of chromosome 15

Prader-Willi syndrome- Micro deletion of chromosome 15

Large deletions will most probably be lethal

Smaller deletions may allow survival

Prader-Willi lack of muscle tone in newborn

poor swallowing reflex

as adult - gross obesity

mean I.Q. ~ 50

microdeletion of 15

developmentally delayed

jerky movements

stiff, fixed smile

uncontrolled laughter

abnormal E.E.G., epilepsy

microdeletion of 15

Deletions (deficiencies)

Duplications

Inversions

Translocations

Redundant segment of a chromosome

A B C D E F G A B C D E F F G

inherited neurological disorder that affects the peripheral nerves. individuals experience weakness and wasting (atrophy) of the muscles

of the lower legs beginning in adolescence; later they experience hand weakness and sensory loss.

caused by having an extra copy (a duplication) of the PMP22 gene. It is inherited in an autosomal dominant manner. Treatment : physical therapy; occupational therapy; braces and other

orthopedic devices; orthopedic surgery; and pain medications.

Deletions (deficiencies)

Duplications

Inversions

Translocations

A B C D E F G H I J K

A B C H G F E D I J K

180O

A portion of the chromosome has

broken off

A B

C

D

E

F G

turned upside down and reattached,

therefore the genetic material is

inverted.

• 180o reversal of chromosome segment

• Produced through breakage and

reassociation of chromosome

A B

C

D

E

F G

Inversions cause complicated synapsis at meiosis for heterozygotes

Those not containing the centromere

are called paracentric.

Chromatids involved in crossing over do not allow development of

functional gametes

Inversions containing the centromere

are called pericentric.

May change phenotype through “position effects”

move active genes to sites generally inactive;

lose gene function

move inactive genes to sites generally active;

gain gene function

May act to preserve blocks of genes (specific alleles) which

function well together

No gain or loss of information; just rearrangement of genome.

Deletions (deficiencies)

Duplications

Inversions

Translocations

Reciprocal Translocation: Exchange of segments between non-homologous chromosomes

F

A

B

C

D

E

L M NO

P

Q

A B C

D E F

O N M L

Q P

segment from one chromosome is exchanged with a segment from another nonhomologous one, so two translocationchromosomes are generated simultaneously.

A portion of one chromosome is transferred to

another chromosome.

Lead to impaired fertility

› complications to synapsis and segregation

May lead to changes in phenotype

› position effects

› human cancers and translocations

A B C

D E F

O N M L

Q P

A B C D E F

L M N O P Q

Only 1/3 of the segregations will lead to

usable gametes

Fertility is reduced by 2/3

Chronic myelocytic leukemia, is a slowly progressing blood

and bone marrow disease that usually occurs during or after

middle age, and rarely occurs in children.

Several human cancers are associated with reciprocal

translocations

Normally, the bone marrow makes blood stemcells (immature cells) that become mature blood cells over time.

A blood stem cell may become a myeloid stem cell ora lymphoid stem cell.

A lymphoid stem cell becomes a white blood cell.

A myeloid stem cell becomes one of three types of mature bloodcells: RBC, platelets and Granulocytes.

Reciprocal translocation between chr. 22 and chr. 9

9 9 22 22

Reciprocal translocation between chr. 22 and chr. 9

9 9 22 22

Chr. 9 segment

has an oncogene;

when moved, it

becomes active

Translocations between chr. 8 and one of three others:› 8 & 2 or 8 & 14 or 8 & 22

Chr. 8 has an oncogene ( genes involved in cell proliferation)

Chr. 2, 14, 22 have genes coding for antibody production and their enhancer genes

Oncogene becomes highly active under control of enhancers!

Fusions

› two chromosomes join to form one

Fissions

• one chromosome splits to form two

Polydyspondylie

› mental retardation and spinal malformations

› fusion of two chromosomes w/ loss of short

arms

Familial Down Syndrome› fusion of chromosomes 14 and 21

14 21 14+21

synapsis

Three possible disjunctions

X

X

X

X

X

X

MYTH: Down syndrome is hereditary and runs in families.

TRUTH:

• Down syndrome is hereditary in approximately 1% of all instances.

• In the other 99% of cases Down syndrome is completely random and the

only known factor that increases the risk is the age of the mother (over

35).

• Translocation is the only type of Down syndrome known to have

hereditary link.

Myths and Truths about Down

Syndrome

Maternal Age:

Women are born with all the eggs they will ever have.

Therefore, when a woman is 30 years old, so are her eggs.

Errors can crop up in the eggs' genetic material as they age over time.

Therefore, older women are more at risk of giving birth to babies with

chromosome abnormalities than younger women.

Since men produce new sperm throughout their life, paternal age does not increase risk of chromosome abnormalities.

MYTH: Children with Down syndrome must be placed in segregated special

education programs.

TRUTH: Children with Down syndrome have been included in regular academic

classrooms in schools across the country.

The current trend in education is for full inclusion in the social and educational

life of the community.

Inclusion is a right, not a privilege for a select few

It is possible to treat diseases by altering our very genes‚giving us new ones if ours are non-functional, changing badgenes for good ones.

Human Genome Project

The primary goal is to determine the sequence of chemical base pairs

which make up human DNA, and to identify and map the total genes of

the human genome from both a physical and functional standpoint.

We need to understand that the “genome” ofindividual is unique. Mapping the human genomeinvolves sequencing multiple variations of eachgene. There is a need to get ready , to facecourageously and to appreciate the truth that mostchromosome abnormalities can occur.

This study is about embracing all, making acommitment to do whatever it takes to provide eachone in the community- an inalienable right to belong,not to be excluded. Assume then, that living andlearning together is a better way that benefitseveryone, not just children who are labeled ashaving a difference.

Thank you for listening…

Enjoy Being Normal!