Bases of human genetic. Method of studying of human heredity

1. Bases of human
genetic.
Method of studying
of human heredity

2. The following methods are applied
to study human genetics
• Genealogical method
• Twins method
• Dermathoglyphic method
• Cytogenetic method
• Biochemical method
• Population statistics method
• Methods of molecular biology and genetic
engineering

3. Genealogical method
•A pedigree is a diagram representing the familial
relationships among relatives. It can be
used to analyze Mendelian inheritance of certain
traits. The symbols have been standardized
•Accurate documentation of the family history is an
essential part of genetic assessment.
Family pedigrees are drawn up and relevant
medical information on relatives sought.

4. Pedigree symbols

5. Sponsored
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6. • It is important to record full names and
dates of birth of relatives on the pedigree,
so that appropriate hospital records can be
obtained if necessary.
• Age at onset and symptoms in affected
relatives should be documented.
• Specific questions should be asked about
abortions, stillbirth, infant death, multiple
marriages and consanguinity

7. • Approximately 65% of human monogenic
disorders are autosomal dominant,
• 25% are autosomal recessive,
• and 5% are X-linked.

8. CHARACTERISTICS OF AUTOSOMAL DOMINANT INHERITANCE
•A vertical pattern is observed in the pedigree, with multiple generations
being affected.
•Heterozygotes for the mutant allele show an abnormal phenotype.
• Males and females are affected with equal frequency and severity.
•Only one parent must be affected for an offspring to be at risk for developing
the phenotype.
•When an affected person mates with an unaffected one, each offspring has a
50% chance of inheriting the affected phenotype. This is true regardless of the
sex of the affected parent—specifically, male-to-male transmission occurs.
•The frequency of sporadic cases is positively associated with the severity of
the phenotype. Autosomal dominant phenotypes are often age dependent,
less severe than autosomal recessive phenotypes, and associated with
malformations or other physical features.
Source: Reproduced from Pyeritz RE. Medical Genetics. In Tierney L, et al. Current Medical Diagnosis
& Treatment, 42nd ed. 2003.

11. CHARACTERISTICS OF AUTOSOMAL RECESSIVE INHERITANCE
•A horizontal pattern is noted in the pedigree, with a single generation being affected.
• Males and females are affected with equal frequency and severity.
•Inheritance is from both parents, each of whom is a heterozygote (carrier) and each of
whom is usually clinically unaffected by his or her carrier status.
•Each offspring of two carriers has a 25% chance of being affected, a 50% chance of
being a carrier, and a 25% chance of inheriting neither mutant allele. Thus two-thirds of
all clinically unaffected offspring are carriers of the autosomal recessive phenotype.
•In matings between individuals, each with the same recessive phenotype, all offspring
will be affected.
•Affected individuals who mate with unaffected individuals who are not carriers have
only unaffected offspring.
•The rarer the recessive phenotype, the more likely it is that the parents are
consanguineous (related).
Source: Reproduced from Pyeritz RE. Medical Genetics. In Tierney L, et al. Current Medical Diagnosis& Treatment, 42nd ed. 2003.

14. CHARACTERISTICS OF X-LINKED INHERITANCE X-LINKED INHERITANCE
•There is no male-to-male transmission of the phenotype.
• Unaffected males do not transmit the phenotype.
• All daughters of an affected male are heterozygous carriers.
• Males are usually more severely affected than females.
•Whether a heterozygous female is counted as affected—and whether the phenotype
is called “recessive” or “dominant”—often depends on the sensitivity of the assay or
examination.
•Some mothers of affected males will not themselves be heterozygotes (i.e., they will
be homozygous normal) but will have a germinal mutation. The proportion of
heterozygous (carrier) mothers is negatively associated with the severity of the
condition.
•Heterozygous women transmit the mutant gene to 50% of their sons, who are
affected, and to 50% of their daughters, who are heterozygotes.
•If an affected male mates with a heterozygous female, 50% of the male offspring
will be affected, giving the false impression of male-to-male transmission. Among the
female offspring of such matings, 50% will be affected as severely as the average
hemizygous male; in small pedigrees, this pattern may simulate autosomal dominant
inheritance.
Source: Reproduced from Pyeritz RE. Medical Genetics. In Tierney L, et al. Current Medical Diagnosis & Treatment, 42nd ed. 2003.

15. Vitamin D-resistant rickets as a dominant X-linked trait:
Hemophila as a recessive X-linked trait:

16. Examples of Sex-Linked Recessive Disorders
• Red/Green Colorblindness – Difficulty perceiving differences
between colors (red or green, blue or yellow).
• Hemophilia – Absence of one or more proteins necessary for
normal blood clotting.
• Cataracts – opacity in the lens that can lead to blindness
• Night blindness – (Nyctalopia) rods do not work so that can not see
in the dark
• Glaucoma – pressure in the eye that can lead to optic nerve
damage and blindness
• Duchenne Muscular Dystrophy – progressive weakness and
degeneration of skeletal muscles that control movement due to
absence of dystrophin (protein that maintains muscle integrity).
Mainly in boys, onset 3-5 years, by 12 years can’t walk, and later
needs respirator.

17. In Y linked inheritance
only males would be affected, with transmission being from a
father to all his sons via the Y chromosome.
This pattern of inheritance has previously been suggested for
such conditions as
-porcupine skin,
-hairy ears,
-webbed toes.

19. Twins method
Twin studies, although limited by
complicating factors, provide the best
source for separating genetic
contributions to the trait being studied
from environmental influences

20. • The classical twin method examines to
what extent genetic and environmental
factors contribute to variation in a trait.
• The premise of the twin method is that
monozygotic (MZ) twins not only share all
their genes, but also their up bringing and
early environment.

21. Conversely, apart from their upbringing and early
environment, dizygotic (DZ) twins share an average of
only 50% of their segregating genes.
Therefore, all phenotypic dissimilarity between MZ
twins is assumed to be due to non-shared
environmental differences between the twins, whereas
dissimilarity between DZ twins is assumed to be due
both to genetic and non-shared environmental
differences.
Consequently, if MZ twins are more similar for a trait
than DZ twins, a genetic contribution to the trait can be
inferred

22. There are two different kinds of
twins;
identical and fraternal.
•Identical twins come from one egg which is
fertilized by one sperm.
•That single fertilized egg, or zygote,then
splits into two separate identical embryos
which continue to grow

23. • Fraternal twins come from
two separate eggs that are
ovulated at the same time.
• In this case the two egg sare
fertilized by two
different sperm.
• Fraternal twins are just like
anordinary brother and sister,
except that they are born at
the same time.
• They have a different genetic
make up and tend to be very
independent of each other.

26. Twin studies are conducted all over the
world,and help to distinguish between what is
influenced by genetics and what is influenced
by environment.
This means that they candeter mine whether a
disorder is something you are born with, or
whether it is some thing that is developed
based on the surroundings

29. HERETABILITY
HC = (CMZ - CDZ)/(100 - CDZ)

30. Dermathoglyphic method
• Dermatoglyphics refers to the branch of
science in the study of the patterns of skin
ridges (dermal ridges) present on the
fingers, palm, toes and the soles of human
In 1892 the English scientist Francis Galton, published his book "Fingerprints" where
he proved that the slim figure on fingertips of any person is unique and therefore can
confidently identify the man.

31. Different types of Loops
• A = Arch
• U= Ulnar loop
• R= Radial loop
• W = Whorl

34. The given method has advantages over
other genetic analysis due to two reasons
1)it is an express method
2)this method doesn’t require high-cost equipment.
Therefore, dermatoglyphics is a very useful link in diagnosing the genetic
abnormalities. But why some diseases make reflection on the dermal picture of
the person. This accordance among some pathologies and fingerprints is
hidden in the embryonic development. The dermal ridges are formed during the
same period when the formation of nervous system takes place. Both papillary
ridges and nervous system structures have common origin in ectoderm (the
outer layer of the early embryo)

35. The study of chromosome number,
structure, function, and behavior in
relation to gene inheritance,
organization and expression
Cytogenetic method

36. • Chromosomal analysis is usually performed on
white blood cell cultures.
• Other samples analysed on a routine basis
includecultures of fibroblasts from skin biopsy
samples, chorionic villi and amniocytes for
prenatal diagnosis, and actively dividing bone
marrow cells.
• The cell cultures are treated to arrest growth
during metaphase or prometaphase when the
chromosomes are visible.

37. INDICATIONS FOR CYTOGENETIC ANALYSIS
• Malformations associated with a particular syndrome or aberration
• Serious mental or physical developmental problems
• Maldefined genitalia (internal or external)
• Primary amenorrhea or delayed pubertal development
• Males with learning or behavioral disorders who are taller than expected
• Malignant or premalignant disease
• Parents of a patient with a chromosome translocation
• Parents of a patient with a suspected syndrome
• Couples with a history of multiple spontaneous abortions of unknown cause
• Infertility not caused by obstetric or urogenital problems
• Prenatal diagnosis
Source: Reproduced from Pyeritz RE. Medical Genetics. In Tierney L, et al. Current Medical Diagnosis & Treatment, 42nd ed. 2003.

38. Routine chromosomal analysis requires the study of
metaphase chromosomes in cultured cells.
Results are usually available in 1–3 weeks.
Molecular genetic analysis by fluorescence in situ hydridisation
(FISH) studies is possible for certain conditions.
These studies are usually performed on cultured cells, but in
some cases (such as urgent prenatal confirmation of trisomy 21)
rapid results may be obtained by analysis of interphase nuclei in
uncultured cells.

39. Why Analyse Chromosomes and Genes?
Genetic errors arise from deletions or insertions of
genetic material, abnormal numbers of whole
chromosomes or genes, and even from misplacement
of a single base in the DNA sequence.
Genetic abnormalities can range from relatively
harmless to severe: from vitamin deficiencies and
food allergies to cancer, birth defects and infant
mortality.

40. Preparing a karyotype
1. Harvested cells are first cultured
2. The cells are then treated with colchicine
which arrests the cells in metaphase, and
then treated and stained to observe the
chromosomes
3. Chromosomes can be photographed or
visualized using a computer, and then
analyzed
4. Chromosomes are identified by size,
position of the centromere, and banding and
staining regions

44. Biochemical method
• Biochemistry is carried out at the cellular or subcellular
level, generally on cell extracts. Biochemical methods
are applied to the main chemical compounds of
genetics—notably DNA,RNA, and protein.
• Biochemical techniques are used to determine the
activities of genes within cells and to analyze substrates
and products of gene-controlled reactions.

45. • In one approach, cells are ground up and the
substituent chemicals are fractionated for further
analysis.
• Special techniques
(e.g., chromatography and electrophoresis) are
used to separate the components of proteins so
that inherited differences in their structures can
be revealed.

46. Specialised biochemical genetic departments offer clinical
and laboratory services for a range of inherited metabolic
disorders.
Tests are undertaken to identify conditions such as disorders
of amino acids, organic acids and mucopolysaccharides,
lysosomal and lipid storage diseases, peroxisomal and
mitochondrial disorders.
Tests for other metabolites or enzymes are performed when
a diagnosis of a specific disorder is being considered

47. Population statistics method

48. Godfrey H. Hardy: English mathematician (1903)
Wilhelm Weinberg: German physician (1908)
W.E. Castle: American geneticist (1908) (left
out)
Working independently just a few years after the
rediscovery of Mendelian genetics they
concluded that:
The original proportions of the allele frequencies
in a population remain constant from generation
to generation as long as five assumptions are m47 et
The Hardy-Weinberg Principle

49. 48
Five –W Eq assumptions:
1. The population size is very large
2. Random mating is occurring
3. No mutation occurs
4. No selection occurs
5. No alleles transfer in or out of the
population (no migration occurs)
Then allele frequencies in the population
will remain constant through future
generations
The Hardy-Weinberg Principle

50. 1) diploid organisms
2) sexual reproducing organisms
3) generations are non-overlapping
4) all genotypes are equally viable
•If these simplifying assumptions are not met, it
complicates the mathematics for the analyses
•Whether or not these assumptions are all met,
biologists can use Mendelian ratios and Hardy-
Weinberg analysis to measure rates of evolution
Simplifying Assumptions for
The Hardy-Weinberg Principle

51. 50
• p = frequency for first allele in the population’s
gene pool
• q = frequency for second allele in the
population’s gene pool
• Calculate allele frequencies with a binomial
equation:
p + q = 1
• because there are only two alleles:
p + q must always equal 1 (100% of the
alleles)
• [Note: more alleles can be handled, e.g., with three alleles: p + q + r = 1]
The Hardy-Weinberg Principle

52. 51
Calculate genotype frequencies with a
binomial expansion
(p+q)2 = p2 + 2pq + q2 = 1
• p2 = individuals homozygous for first allele
• 2pq = individuals heterozygous for the
alleles
• q2 = individuals homozygous for second
allele
• because there are three phenotypic classes:
p2 + 2pq + q2 must always equal 1
The Hardy-Weinberg Principle

53. 52
1. The population size is very large
2. Random mating is occurring
3. No mutation occurs
4. No selection occurs
5. No alleles transfer in or out of
the population (no migration)
Then allele frequencies in the population
will remain constant through
generations
The Hardy-Weinberg
Equilibrium

54. If any conditions of Hardy-Weinberg not
met:
• Genotype frequencies change
• Evolution occurs!
• Evolution = change in gene
frequency of a population over
time.

55. Molecular biology in medicine
•Medicine utilizes molecular biology
products and techniques in analysis
of disease, disease genes and gene function
•Early stage diagnostics, new disease
biomarkers
• New vaccines and medicines
• Gene therapy
• Personalized medicine

56. Techniques of Molecular Genetics
• Recombinant DNA Technology—Genetic
Engineering—Biotechnology:
• Locating, isolating, altering, and studying DNA
segments
• Biotechnology:
• Using recombinant DNA technology to
develop new biological products

57. Biotechnology Harnesses the
Power of Molecular Genetics
• Pharmaceuticals
• Human insulin
• Specialized bacteria
• Agricultural products
• Oligo nucleotide drugs
• Genetic testing
• Gene therapy
• Direct transfer of genes into humans to
treat disease

58. What is a genetic consultation?
A genetic consultation is a health service that
provides information and support to people who
have, or may be at risk for, genetic disorders.
During a consultation, a genetics professional
meets with an individual or family to discuss
genetic risks or to diagnose, confirm, or rule out
a genetic condition.

59. The reasons that a person might be referred to a genetic
counselor, medical geneticist, or other genetics
professional include:
• A personal or family history of a genetic condition, birth
defect, chromosomal disorder, or hereditary cancer.
• Two or more pregnancy losses (miscarriages), a still
birth, or a baby who died.
• A child with a known inherited disorder, a birth defect,
mental retardation, or developmental delay.

60. • A woman who is pregnant or plans to become pregnant at or
after age 35. (Some chromosomal disorders occur more
frequently in children born to older women.)
• Abnormal test results that suggest a genetic or
chromosomal condition.
• An increased risk of developing or passing on a particular
genetic disorder on the basis of a person’s ethnic background.
• People related by blood (for example, cousins) who plan to
have children together. (A child whose parents are related
may be at an increased risk of inheriting certain genetic
disorders.)

61. During a consultation,
a genetics professional will:
• Interpret and communicate complex
medical information.
• Help each person make informed,
independent decisions about their health
care and reproductive options.
• Respect each person’s individual beliefs,
traditions, and feelings.

62. A genetics professional will NOT:
• Tell a person which decision to make.
• Advise a couple not to have children.
• Recommend that a woman continue or
end a pregnancy.
• Tell someone whether to under go testing
for a genetic disorder.