Different mode and types of inheritance Lecture 6

Definition Allelle is an alternative form of a gene (one member of a pair) that is located at a specific position on a specific chromosome. These DNA coding determine distinct traits that can be passed on from parents to offspring. The process by which alleles are transmitted was discovered by Gregor Mendel and formulated in what is known as Mendel’s law of segregation.

Definitions Genotype Inheritance Is the structures of the genes Inheritance Genetic trait or characteristic that is passed on from a parent to the next generation of offspring Dominant genes are most often expressed as observable characteristics. Recessive genes are most often masked by the dominant genes, unless the offspring inherits one of the same recessive gene from each parent.

Definitions Homozygous means that the two alleles an individual possesses for one gene are the same i.e. AA or aa Heterozygous means that the two alleles an individual possesses for one gene are different i.e. Aa

MODE Mode of inheritance Inheritance patterns describe how a disease is transmitted in families. These patterns help to predict the recurrence risk for relatives. These disorders are called Mendelian disorders, after the geneticist Gregor Mendel.

Mode and types of inheritance Single Gene Inheritance Autosomal dominant Autosomal recessive X-linked Multifactorial Inheritance Mitochondrial Inheritance

Single gene inheritance When a certain gene is known to cause a disease (mutation), we refer to it as a single gene disorder. Examples: cystic fibrosis, sickle cell disease. Types Autosomal dominant Autosomal recessive X-linked

Single autosomal dominant gene Autosomal dominant means that a person only needs one copy of the changed gene (genetic difference) in order to have the disorder (heterozygous). Usually, the changed gene is inherited from a parent who also has the disorder and every generation in the family may have members with the disorder. There are some instances in which a person has the gene that causes the disorder and does not show symptoms of the disorder, but can still pass the gene to his or her children. A person who carriers a gene for an autosomal dominant disorder has a 50% chance of passing the gene to each child.

Single autosomal dominant gene - conditions that are manifest in heterozygotes (individuals with just one copy of the mutant allele).

Examples for Autosomal dominant diseases Inherited colon cancer Inherited breast cancer

SINGLE AUTOSOMAL RECESSIVE GENE Autosomal recessive means that it is necessary to have two copies of the changed gene to have the disorder (homozygous). Each parent contributes one changed copy of the gene to the child who has the disorder. The parents are called carriers of the disorder because they have one normal copy of the gene and one changed copy of the gene, but they do not show symptoms of the disorder. When both parents are carriers of the changed gene, each of their children has a 25% chance of having the disorder, a 50% chance of being a carrier of the disorder (like their parents), and a 25% chance of neither being a carrier nor having the disorder (These risks are the same for each pregnancy).

SINGLE AUTOSOMAL RECESSIVE GENE - conditions are only manifest in individuals who have two copies of the mutant allele (are homozygous).

At conception each child of parents who are both carriers has: Examples for Autosomal Recessive diseases Spinal muscular atrophy Congenital deafness At conception each child of parents who are both carriers has: 1 in 4 (25%) chance of being an unaffected non-carrier; 2 in 4 (50%) chance of being a carrier 1 in 4 (25%) chance of inheriting the condition.

Comparison of autosomal dominant and recessive modes of inheritance Autosomal recessive Disease express in heterozygote Disease expressed in homozygote On average half of offspring affected Low risk to offspring Equal frequency and severity in each sex

Sex linked inheritance X-linked disorders are those in which the defective gene lies on the X sex chromosome This is the reason why a male who carries an abnormal gene on his single X chromosome will express clinical signs of disease (X-linked disorders are most common in males as there is no second X chromosome carrying the normal copy to compensate) whereas a woman who has an abnormal gene on only one of her X chromosomes will be a carrier. (Females are less likely to be affected as they have the non-affected X chromosome as well)

Sex linked inheritance X-linked dominant inheritance It follows a pattern similar to autosomal dominant inheritance except that more females are affected than males. However, X-linked dominant disorders are very rare.

Sex linked inheritance X-linked recessive disorders usually only seen in males and they are much more common than X-linked dominant disorders. People with an X-linked recessive disorder do not have any normal copies of the gene. Males only have one X chromosome, so if a male inherits a changed gene on his X chromosome (which is always inherited from his mother), then he does not have another copy of the working gene to compensate. Females with one copy of a changed gene on one X chromosome are called carriers of X-linked recessive disorder. It is rare for a female to have the changed gene on both her X chromosomes.

Sex linked inheritance X-linked recessive disorders In most cases, females who are carriers do not show symptoms because the working copy of the gene compensates for the non-working copy of the gene. Examples of X-linked recessive conditions include: Haemophilia (is inherited genetic disorder that impairs the body's ability to make blood clots) Duchenne muscular dystrophy (is a genetic disorder characterized by progressive muscle degeneration and weakness.)

Examples for sex-linked inheritance non-carrier father and a carrier mother Sons - 50% chance of being affected Daughters - 50% chance of being carriers.

Examples for sex-linked inheritance When the mother is a carrier for an X-linked recessive condition, Each daughter has a 1 in 2 (50%) chance of inheriting the gene alteration and so being a carrier for the condition.  Each son has a 1 in 2 (50%) chance of inheriting the gene alteration and so inheriting the condition.  When the father has an X-linked condition: his sons will not be affected.  His daughters will be a carrier for the condition (100%). Males transmit their Y chromosome to their sons.  This means that sons will not inherit an x-linked recessive condition from their father.

Multifactorial inheritance

Multifactorial conditions

Mitochondrial inheritance

Mitochondrial inheritance The transmission of the mitochondrial genome from mother to child. WHY? Since egg cells, but not sperm cells, keep their mitochondria during fertilization, mitochondrial DNA is always inherited from the female parent. Causes: mutations in the non-nuclear DNA of mitochondria. Both males and females are equally affected

Mitochondrial inheritance Since many mitochondria are passed into the egg from the cells in the ovary, all the offspring of an affected woman would be expected to inherit the condition. An affected male does not pass on his mitochondria to his children, so all his children will be unaffected.  This is called mitochondrial (sometimes matrilineal) inheritance. As a mitochondrial condition is caused by incorrectly functioning mitochondria, it may be due to: - an alteration in the nuclear DNA (e genome) - an alteration in the mitochondrial DNA

Examples of mitochondrial inheritance an eye disease called Leber's hereditary optic atrophy; a form of dementia called MELAS for mitochondrial encephalopathy, lactic acidosis and stroke-like episodes.

summary Single Gene Inheritance Multifactorial Inheritance Changes or mutations occur in DNA sequence of a single gene Multifactorial Inheritance A combination of environmental factors and multiple gene Mitochondrial Inheritance Mutations in the non-nuclear DNA mitochondria