The document discusses human genetics and chromosome abnormalities. It covers several key points: 1) It describes the basic components and structure of chromosomes and DNA. This includes the number and types of chromosomes in human cells. 2) It explains different types of chromosome abnormalities including numerical abnormalities (aneuploidy, polyploidy) and structural abnormalities (deletions, duplications, inversions, translocations). 3) It discusses several patterns of inheritance for genetic conditions including autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance.

4.  The etiology of all human diseases can be
attributed to
• Genetic factors,
• Environmental factors
• Mixture of both
• The application of Genetics as a science and its
new post-modern extensions, the Molecular
Genetics and the Molecular Medicine, are critical
to all manners of diseases in all stages of life.

5.  Chromosomes are present in all nucleated
cells & contain DNA with its hereditary
information.
 Chromosomes are mostly studied in
peripheral blood lymphocytes, but also in any
growing tissue including bone marrow, skin
fibroblasts or amniotic fluid cells

6. DNA is formed of
three building
blocks;
• A pentose sugar
(deoxyribose)
• Phosphate group
• Nitrogenous bases
 purines, adenine and
guanine;
 pyrimidine, thymine and
cytosine.

7. Every human cell has 23
pairs of chromosomes.
One copy of each
chromosome is inherited
from each parent.
Twenty-two pairs of
chromosomes are
autosomes; the remaining
pair is called the sex
chromosomes.

8.  They all have a short arm p
and long arm q. separated
by a primary constriction
called the centromere.
 The centromere is the
location of spindle
attachment and is an integral
part of the chromosome. It is
essential for normal
movement and segregation
of chromosomes during cell
division.

9.  Genes are the individual units of
heredity for all traits
 Typical gene contains a promoter
sequence, an untranslated region,
and an open reading frame,
 In the open reading frame, every
three nucleotides represent a single
codon, which codes for a particular
amino acid.
 The complete set of genes of
the human cell and the
intervening DNA sequences is
called the human genome

10. Each gene has a defined function
 Structural genes: synthesis of specific
polypeptide chains that conduct particular
metabolic function (enzymes, hormones,
immunoglobulins,….etc.
 Regulatory genes: regulate & control
functions of structural genes.
 Repair genes: keep structural integrity of
DNA & repair damage in it.

11.  Chromosome abnormalities usually occur
when there is an error in cell division during
meiosis or mitosis.
 There are many types of chromosome
abnormalities.
 They can be organized into two basic groups,
numerical and structural abnormalities.

12. Aneuploidy
 When an individual is missing either a chromosome from a pair
(monosomy) or has more than two chromosomes of a pair (trisomy).
• Down Syndrome,
• Turner Syndrome
 Polyploidy:
 the number of chromosomes is the multiple of the
haploid number (i.e., 23 chromosomes). Usually, this
anomaly is incompatible with life.

13. When the
chromosome's
structure is altered.
 Deletions
 Duplications
 Inversions
 Rings
 Translocations:
• Reciprocal translocation
• Robertsonian
Isochromosome
 Chromosome
instability
syndromes

15. • It is the term used to describe an individual who has
two or more different cell lines derived from a single
zygote (fertilized egg). This usually arises during early
embryogenesis.
• Germ line mosaicism: refers to the presence of
mosaicism in germ cells found in gonads. In this case
there is an increases risk of recurrence of an affected
child.

16.  Most chromosome abnormalities occur as an
accident and are therefore not inherited.
 The abnormality is present in every cell of the
body.
 Some abnormalities, can happen after
conception, resulting in mosaicism
 Chromosome abnormalities can be inherited
from a parent or be "de novo".

17. Mendalian genes can be inherited in many ways:
 Autosomal dominant
 Autosomal recessive trait
 X-linked recessive traits
 X-linked dominant inheritance
 Mitochondrial inheritance
• Encephalopathy, myopathy
• Transmission exclusively through females (by ova)

18. Autosomal dominant disorders are those
disorders in which a single gene in the
heterozygous state is sufficient to cause
the phenotype.
Autosomal dominant disorders are often
caused by mutations in genes coding for a
structural protein.

19.  Mutant gene is inherited from one parent
who is affected by the same condition.
 The disorder appears in a vertical
manner in the pedigree with affected
individuals are present in every
generation.
 Phenotypically normal family members
do not transmit the disorder their
offspring.
 Males and females are equally affected.
 Both males and females can pass the
abnormal gene to children of either sex.

20.  Affected individual passes the
mutant gene to 50% of their
offspring, (1:2 for each
pregnancy).
 In cases of fresh mutation the
recurrence risk is very low

21. Spherocytosis
Achondroplasia
Tuberous sclerosis
Marfan syndrome
Myotonic dystrophy
Neurofibromatosis I
Osteogenesis imperfecta

22. Autosomal recessive disorders are those
disorders in which two copies of the mutant
gene in the homozygous state are necessary
to cause the phenotype.
Autosomal recessive disorders are caused by
mutations that frequently affect genes
encoding for enzymes, i.e. result in metabolic
disease.
New mutation is less common than in
autosomal dominant disorders.

23.  The mutant gene must be inherited from
both parents for the phenotype to be
expressed.
 Both parents of the affected child are
asymptomatic heterozygous carriers for
the gene.
 Inheritance is horizontal; the affected
individuals are almost always born in
only one generation of the family, i.e.
siblings not father or mother is affected.
 Males and females are equally affected.
 Both males and females can pass the
abnormal gene to children of either sex.

24.  Each child of two heterozygous carrier parents has a 25%
chance of being homozygous (i.e. phenotypically
affected). Therefore, recurrence risk for siblings (1:4 for
each pregnancy).
 The prevalence of carriers for certain autosomal
recessive disorders
• African population: sickle cell anemia (up to 25% of the
population)
• Northern European: cystic fibrosis (up to 4% of the
population)
• Mediterranean population: Thalassemia (up to 17% of
the population)
• Ashkenazi Jews: neurodegenerative disorders Tay
Sachs disease (up to 4% of the population)

25. •α1-antitrypsin
• Cystic fibrosis
• Sickle cell disease
• Thalassemias
• Storage diseases

26.  X-linked inheritance occurs when an individual inherits
a mutant gene on X chromosome.
 Generally, the severity of disorders inherited as X-
linked is greater in males than in females
 Affected male pass the disease only to his daughters
and not for to his sons.
 Affected females pass the disease to both her
daughters and sons.

27.  Manifests in both heterozygous female & hemizygous male
 Affected female: half daughters & half sons
 Affected male: all daughters, none of sons
 Recurrence risk
 The risk of recurrence for the offspring of heterozygous female is 50%
regardless of the sex.
 The risk of recurrence for the offspring of homozygous female is 100%
regardless of the sex.
 The risk of recurrence for the offspring of a male is 100% for his
daughters and 0% for his sons.
Common example
• Vitamin D resistant rickets,
• Incontinentia pigmenti

28. XX XY
XX XY XX XY
Affected male: all daughters, none of son
XX XY
XX XY XX
XY

29.  X-linked recessive disorders occur due to inheritance of a mutant allele of
a gene on X chromosome.
 For disease expression in males it is enough to inherit one mutant allele
on the single X chromosome in males since the Y chromosome have no
normal allele to compensate for the muted gene.
 Two mutant alleles must be present in females in order for the disease to
be expressed.
 Heterozygous females (carriers) are either normal or have mild
manifestations.
 Homozygous females are very rare.
 New mutation rate may happen in as high as one third of cases; i.e. there
is a significant proportion of sporadic cases.

30. Recurrence risk in X-
linked recessive
disorders differ
depending on whether
the mother or the
father has the mutant
gene:
Examples
Hemophilia A
G-6-PD deficiency
Duchenne muscle
dystrophy

31. XX XY
XX XY XX XY
Affected male: all daughters carriers sons free
XX XY
XX XY XX
XY

32. XX XY
XX XY XX XY
Hetrognous female& diseased male: half daughters
diseased, half sons diseased half daughter carriers
half sons free.
XX XY
XX XY XX
XY

33.  Traits that are due to combination of many
genetic & non-genetic environmental factors.
 Some factors have to be considered: sex,
biological relation, consanguinity, and severity of
trait.
 Disorders include
• Congenital malformation e.g. cleft lip/palate,.
pyloric stenosis, CHD
• Acquired: asthma, DM, hypertension, epilepsy,
depression, schizophrenia

34. Family Pedigree

35. Quiz: Family Pedigree

36. Quiz : Family Pedigree
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37. Quiz : Family Pedigree
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38. Quiz : Family Pedigree
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39. Quiz : Family Pedigree
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