patterns of-inheritance

patterns of inheritance

The objectives of this presentation are to:
Understand how genes are inherited
Understand the differences between the inheritance patterns associated with Autosomal dominant, Autosomal recessive, X-linked recessive and chromosomal abnormalities
Understand that the environment can impact on some common complex conditions
Karyotypes
To analyze chromosomes, cell biologists photograph cells in mitosis, when the chromosomes are fully condensed and easy to see (usually in metaphase).
The chromosomes are then arranged in homologous pairs.
The homologous pairs are then placed in order of descending size. The sex chromosomes are placed at the end.
A picture of chromosomes arranged in this way is known as a karyotype.
The karyotype is a result of a haploid sperm (23 chromosomes) fertilizing a haploid egg (23 chromosomes).
The diploid zygote (fertilized egg) contains the full 46 chromosomes. (in humans)
Normal Human Male Karyotype: 46,XY
Normal Human Female Karyotype: 46,XX
So how are genes passed on from parent to child?
Genes in the cell nucleus are physically located on 23 pairs of chromosomes
One set of 23 chromosomes is inherited from each parent
Therefore, of each pair of genes, one is inherited from a person’s mother, and one from their father




Single Gene – Red represents altered gene in 1st top left pair of Chromosomes 1 altered and 1 unaltered – individual may or may not be affected by this (unless this is a dominant alteration)
2nd pair shows both genes altered – individual will be affected
3rd pair show the sex chromosomes with one alteration but as this is a male XY and the alteration is on the X the male will be affected as there is no counterbalance on the Y chromosome
Some medical conditions are caused by a change in just one or both copies of a particular pair of genes. These are called “single gene disorders”.
The three common types of single gene disorders are called:
Autosomal dominant
Autosomal recessive
X-linked
AD – always expresses itself
AR - only expresses in the absence of dominant unaltered gene – healthy carrier


X – genes found on X chromosomes

Hetero means ‘different’, homo means ‘same’

Homozygotes – received an affected chromosome from each parent who may have been healthy unaffected carriers
X-linked – always affected as they don’t have an X to balance the affected chromosome
Multifactoral – Genes rarely act alone e.g. Height they may have the gene for tall but if malnourished may be short. Changes in both genes can have different variants for example the gene for skin colour not just black and white but shades and environment Sun adding further colour or damage.
Chromosomal – Session 1 reminder extra chromosomes plus insertions and deletions


On a pedigree:
A circle represents a female
A square represents a male
A horizontal line connecting a male and female represents a marriage
A vertical line and a bracket connect the parents to their children
A circle/square that is shaded means the person HAS the trait.
A circle/square that is not shaded means the person does not have the trait.
Children are placed from oldest to youngest.
A key is given to explain what the trait is.

SINGLE GENE INHERITANCE

Autosomal Dominant:
Vertical pattern: multiple generations affected
Males and females equally likely to be affected
See male to male transmission
Each child of an affected individual has a 50% chance to be affected
Unaffected individuals do pass on the gene
Every affected child has an affected parent
Examples of Autosomal Dominant Conditions
Huntington disease
Neurofibromatosis type 1
Marfan syndrome
Familial hypercholesterolemia
Familial Adenomatous Polyposis (FAP)
Prader-willi


Autosomal Recessive:
Horizontal pattern: single generation affected.
Males and females equally likely to be affected
Parents of affected child are unaffected gene carriers and have
a 1 in 4 or 25% recurrence risk
Unaffected siblings have a 2/3 or 67% chance to be carriers.
Children of affected individuals are obligate carriers.
Need both genes in an altered state to show the condition.
Examples of Autosomal recessive conditions
Sickle Cell disease
Cystic fibrosis
Batten Disease
Congenital deafness
Phenylketonuria (PKU)
Spinal muscular atrophy
Recessive blindness
Maple syrup urine disease

X-linked

X-linked Recessive inheritance:
Males are more often affected than females
Affected males pass the gene to all of their daughters and none of
their sons (NO male-to-male transmission)
Daughters of carrier females have a 50% chance to be unaffected
carriers. Sons of carrier females have 50% chance to be affected.
Affected males in the family are related to each other through carrier
females (“Knight’s move”)
For genetically lethal X-linked conditions, 1/3 of isolated cases (i.e. no family history) are new mutations.
In 2/3 of cases, the mother is an unaffected carrier
Female gene carriers are usually not affected
Exceptions: Turner syndrome, skewed X-inactivation, X;autosome translocation carriers
Female – and may also be affected but this may be reduced depending on the gene involved
One copy of an altered gene on the X chromosome causes the disease in a male.
Examples of X-Linked Recessive Conditions
Fragile X syndrome
Haemophilia
Duchenne muscular dystrophy (DMD) (Becker BMD)
Fabry disease
Retinitis pigmentosa
Hunter syndrome
Ocular albinism
Adrenoleucodystrophy.


X-linked Dominant inheritance:
For rare conditions, females are about 2x as likely to be affected than
males. May be lethal in males and usually milder, but variable,
in females.
Affected males pass the gene to all of their daughters, who will be
affected, and to none of their sons (NO male-to-male transmission)
Sons and daughters of affected females have 50% chance of being
affected (similar to autosomal dominant)
POLYGENIC INHERITANCE
Single gene disorders are quite rare
Single gene disorders either give risk to a condition or they don’t
The additive effects of 2 or more genes leading to a continuous variation rather than the either /or of a single gene
Most traits are Polygenic’ i.e. 1 trait coded by a number of altered and unaltered genes working together
Common Polygenic Disorders
Alzheimer's
Diabetes
Cancer
Eczema
MULTIFACTORIAL INHERITANCE
Inheritance controlled by many genes plus the effects of the environment
Genes rarely act alone and both single and polygenic can be multifactoral
Congenital malformations
Cleft lip/palate
Congenital hip dislocation
Congenital heart defects
Neural tube defects
Pyloric stenosis
Talipes
Adult onset disorders
Diabetes mellitus
Epilepsy
Glaucoma
Hypertension
Ischaemic heart disease
Manic depression
Schizophrenia


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تمت الاطفال بحمد الله

FOR FUN
Summary of a year named 5th stage :Mnemonic for branches and subjects studied in 5th stage*** " #MORE_DRUG_PO "***Medicine.Orthopedic (# also refer to fracture and in turn orthopedic).Rheumatology.ENT.Dermatology.Radiology.Urology.Gynecology.Plastic; Pediatric ; Psychiatry ; PHC.Ophthalmology.Notes:*PO = per oz =orally*it is a mnemonic and a Hach_tag since # sign indicate fracture and in turn orthopaedic*remember "more drug" cause drug over dose and that make u sick; well that literally happen to u in 5 th stage u got sick from lecture and exam over dose.Best wishesby my fingertipsDr.Earnest