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Changes in DNA that affect genetic information

 Point Mutations – changes in one or a few nucleotides
 Substitution


THE FAT CAT ATE THE RAT
THE FAT HAT ATE THE RAT
 Insertion


THE FAT CAT ATE THE RAT
THE FAT CAT XLW ATE THE RAT
 Deletion
 THE FAT CAT ATE THE RAT
 THE FAT ATE THE RAT

 Frameshift Mutations – shifts the reading frame of the genetic message so that the protein may not be able to perform its function.
 Insertion


THE FAT CAT ATE THE RAT
THE FAT HCA TAT ETH ERA T
 Deletion

 TEF ATC ATA TET GER AT
H

 Changes in number and structure of entire chromosomes
 Original Chromosome ABC * DEF
 Deletion AC * DEF
 Duplication
 Inversion
 Translocation
ABBC * DEF
AED * CBF
ABC * JKL
GHI * DEF

•
•
Most are neutral
•
• Eye color
Birth marks
Some are harmful
•
• Sickle Cell Anemia
Down Syndrome
• Some are beneficial
•
• Sickle Cell Anemia to Malaria
Immunity to HIV

 There are two ways in which DNA can become mutated:
 Mutations can be inherited.
 Parent to child
 Mutations can be acquired.


Environmental damage
Mistakes when DNA is copied

 Down Syndrome
 Chromosome 21 does not separate correctly.


They have 47 chromosomes in stead of
46.
Children with Down
Syndrome develop slower, may have heart and stomach illnesses and vary greatly in their degree of inteligence.

 Cri-du-chat
 Deletion of material on 5 th chromosome
 Characterized by the cat-like cry made by cri-du-chat babies
 Varied levels of metal handicaps

 Klinefelter’s Syndrome
 XXY, XXYY, XXXY
 Male
 Sterility
 Small testicles
 Breast enlargement

 XYY Syndrome
 Normal male traits
 Often tall and thin
 Associated with antisocial and behavioral problems

 Turner’s Syndrome
 X
 Female
 sex organs don't mature at adolescence
 sterility
 short stature

 XXX
 Trisomy X
 Female
 Little or no visible differences
 tall stature
 learning disabilities
 limited fertility


Bad news: 10 minutes 

Dismorphology)

Types of
Abnormalities :
• Minor anomalies
• Major anomalies
 Malformation
 Disruptions
 Deformations
 Syndromes

Developmental stage at the time of exposure
Dose and duration of exposure to a teratogen

 Hereditary (Genetic) causes 15-18%
 Environmental factors 7-10%
 Multifactorial 25%
 Unknown 50%

 First week (Resistant period)
 Embryonic period

Maximum susceptibility (organ morphogenesis)
 Fetal Period

Lowered Susceptibility (functional derangement)

) Numerical Chromosomal Anomalies (
Polyploidy
69
92
Triploidy
Tetraploidy
Aneuploidy
(Patau syndrome) 13
) Edwards syndrome (
) Down syndrome (
18
21
) Klinfelter syndrome-XXY (
Triple X (Superfemale)
) Turner syndrome- 45,XO (

Patau Syndrome 1/20000 cleft-lip-baby

Edwards Syndrome 1/5000

 Down syndrome
 Maternal nondisjunction (95%)
 Mosaism
 Translocation

•Monosomy
•Nondisjunction in sperm (80%)
•X chromosome only
•Nondisjunction in mitosis (Mosaicism
)

Structural Chromosomal Anomalies


Isochromosome
Crossing over :
 Translocation
21,13,14, 15 in D own syndrome


Partial Deletion
Cri du chat
5 (microcephal, mental, cardiovas)
Microdeletion

Angelman 15 (speech, mental, movement)
Prader- willi 15 (fatty, mental, hypogonad)
Inversion

Gene Mutation Anomalies










Marphan syndrome
Crigler-Najjar syndrome
Roberts syndrome
Alport syndrome
Aarskog-Scott syndrome
Savant syndrome
Treacher-Collins syndrome
Niemann–Pick disease
Cystic Fibrosis
DMD

Environmental factors
•
(& other disease)
•
(& Hormonic Agents)
•
•

Infectious Agents
 A) Viral infections
 Rubella virus (German Measles)
1month-From placentaatrioventricular septsl defect, cataract. Weight ↓
 Cytomegalovirus(CMV)
From Placenta,Cervix,Vagina (& Lactation) microephaly, deafness, mental retardation, hepatospleenomegally ,cardiac defect,cerebral calcification, blue spot on skin
 Herpes simplex virus(HSV)
From Placenta,Vagina(85%)Defect in CNS,liver, pancreas,ren,suprarenal glands, infection on skin, Eyes or mouth – no treatment=40-50% death
 Varicella-zoster virus(VZV) first 3 month-From Placentalimb hypoplasia & parasis., hydrocephaly. Mental retardation, cataract
 HIV
After 35 th weekSystematic Chronic infection(fungus,bacterial,viral,protozoan)

Infectious Agents
 B) Nonviral infections
 Toxoplasma in each three munth - death, microcephaly, hydroceohaly, cerebral calcification
 Treponema pallidum
Syphilis, rhinitis, eye defect
(cataract), icterus,a bnormal teeth, splenohepatomegaly

 Chronic Diseases
 Diabetes
Coudal disgenesis, death
 PKU mental retardation, microcephaly, cardiac defect
 Nutrient deficiency
Iodine deficiency coused cretinism
 Obesity
ONTD, cardiac defect, …
 Hypoxy

 Category X drugs
 Category D drugs


Category X drugs
Thalidomide  Clomiphen
 Aminopterin
 methotrexate
 Busulfan
 Phenytoin
 Triazolam
 Warfarin
 Isotretinoin
 Diethylstilbestrol
 Ethisterone
 Norethindrone
 Nicotine
 Alcohol


Category X drugs
Thalidomide





 Thalidomide

 Aminopterin
 Methotrexate
 Busulfan
Category X drugs
 Used in chemotererapy
 Dawerfism
 Myelomeningocele
 palate clef
 Growth retardation
 ophtalmic defect

Category X drugs
 Aminopterin
 Methotrexate
 Busulfan
 Used in chemotererapy
 Dawerfism
 Myelomeningocele
 palate clef
 Growth retardation
 ophtalmic defect

Category X drugs
 Phenytoin
 Antileptic drug
 microcephaly
 Growth & mental retardation
 palate clef
 Finger & nail Hypoplesia
 Skull defect

Category X drugs
 Warfarin
 Anti couagulant drug




Mental retardation microcephaly optic n. atrophy
Fetal bleeding

Category X drugs
 Clomiphen
 Non-steroidal drug
 Used for stimulus ovulation
 Maybe Malformatin

Category X drugs isotretinoin, 13-cis-retinoic acid
 Retinoids (vitamin A)
 Used for Cystic acne
 severe craniofacial defects
 cardiac defects
 neural tube defects (NTD)
 Palate cleft tretinoin (Retin-A)

Category X drugs





Mental retardation
Wheight loss
Fetal Hypoxy
Premature Parturition

Category X drugs

 Fetal Alcholic Syndrome (FAS)
 Mental retardation
 microcephaly
 Cardivascular defect
 Limb & Face malformation
 Hairsutism

Category D drugs
 Tetracycline
 Valsuroic acid
 Diazepam
 doxycycline
 lorazepam
 Streptomycin
 Lithium
 Phenobarbital
 Hydrochlorothiazide
 Pentobarbital

Category D drugs
 Phenobarbital &
Pentobarbital
 paliative drug
 Fetal malformation

Category D drugs
 Diazepam ,
Lorazepam ,
Chlorodiazepoxide
 antianxiety drug
 palate & lip clef specially in first 3 months

Category D drugs
 Lithium ,Phenothiazine
 Antiedepressive
 CardioVascular defect

(heavy metals)

 Chromosomal defects & Mutation in germ cells
 Environmental agent : transmission of paternal mediated toxicity through seminal fluid

 Ultrasonography
 Maternal Serum Screening (AFP,hCG)
AFP : Trisomy ↓NTD,GIT atresia,amniotic band ↑
 Amniocentesis
 Chorionic Villus Sampling (CVS)

 Fetal Transfusion
 Fetal Medical Treatment
 Fetal Surgery
 Stem Cell Transplantation and Gene Therapy
Befor 18 th week (activation of immune system)