genetics in humans

When I was studying medicine, I had to do an analysis about the genetics that I want to share with you. I hope you like it and it will be very useful. You will understand many things:
PATTERNS OF MONOGENIC HERITAGE
MONOGENIC diseases due to mutations in a single gene and segregate in the family following the laws of Mendel, in fixed proportions according to the type of union, so they are also called MENDELIAN.
So far more than 8,000 monogenic phenotypes have been described according to Victor McKusick's classic work "Mendelian Inheritance in Man", today OMIM as it is ON LINE
CLASSIFICATION OF THE MODE OF TRANSMISSION OR PATTERNS OF CLASSICAL INHERITANCE OF THE MONOGENIC CHARACTERS

AUTOSOMICO:
Autosomal dominant:
Autosomal recessive
LINKED TO THE CHROMOSOME X:
Linked to the dominant chromosome x:
Linked to the recessive chromosome x:
Dominant phenotype is expressed only when one of a pair of chromosomes carries the mutant allele and the other chromosome has a natural allele at the corresponding locus.
Recessive phenotype is expressed only when both chromosomes are carriers of a pair of mutant alleles at a locus.
DOMINANT AUTOSOMICAL INHERITANCE PATTERN
The risk of recurrence will be 50% in each pregnancy
Criteria of the autosomal dominant inheritance pattern

Affected individuals usually have an affected parent (Except in cases of neomutation or reduced penetrance)
The descendants of a couple, in which one is an affected heterozygote and the other a normal homozygote have a probability of 50% of inheriting the character
Phenotypically normal members of a family do not transmit the phenotype to their children (Except in cases of reduced penetrance)
Males and females have the same probability of transmitting the phenotype to their children of any sex
REDUCED PENETRANCE:
Penetrance is the ability to express a gene.
When an individual who possesses the appropriate genotype does not express it, it is said that it has a reduced or incomplete penetrance.
In statistical terms it is the proportion of individuals with a certain genotype that express it in the phenotype.
VARIABLE EXPRESSIVITY
Expressivity is the degree of expression of a phenotype, which when it differs in individuals that have the same genotype is called variable expressivity.
AUTHENTICAL RECESSION INHERITANCE PATTERN
The descendants of a heterozygous marriage have a recurrence risk of 25%.
The descendants of a marriage between a homozygous recessive affected and a dominant homozygous healthy, will not suffer from the disease but will be carriers.
The descendants of a couple between a patient and a carrier will have a 50% risk of expressing the disease.
CRITERIA OF THE RECESSIVE AUTOSOMICAL INHERITANCE PATTERN
Individuals expressing a recessive phenotype are usually children of healthy parents, but obligate carriers of the mutated allele.
The probability of having children that express the phenotype in the offspring of a marriage of carriers is 25%
The parents of the affected individuals are often consanguineous
Males and females have the same probability of presenting the affected phenotype.
PLEIOTROPY: A gene's ability to produce apparently unrelated phenotypic manifestations in various tissues and organs.
ALLELIC HETEROGENEITY: In the fibrocystic disease have been described more than 400 different mutations in the gene CFTR that cause an equal pathological picture, this phenomenon by which different mutations of a single gene produce a similar clinical picture is called allelic heterogeneity.
GENETIC HETEROGENEITY: It is when mutations in different genes produce an identical clinical picture.
PATTERN OF INHERITANCE LINKED TO CHROMOSOME X RECESSIVE
50% of males will be affected and 50% of female carriers.
CRITERIA FOR INHERITANCE LINKED TO X RECOMMENDED CHROMOSOME

The disease is expressed more frequently in the male sex
The mutated gene is transmitted by the affected man to all his daughters who will be carriers and in turn will transmit it to 50% of his sons who will express the disease
Affected males do not transmit their mutated gene to their male children
Affected males transmit the disease to their male grandchildren through their carrier daughters
Heterozygous women are usually not affected, but can express the phenotype moderately
PATTERN OF INHERITANCE LINKED TO THE DOMINANT X CHROMOSOME
In the offspring of a woman affected by a disease linked to the dominant X chromosome, the children are male or female will have a risk of suffering from the disease of 50%.
The offspring of a man affected by a disease linked to the dominant X chromosome, all females will be diseased and healthy males.
CRITERIA FOR INHERITANCE LINKED TO THE KEY CHROMOSOME X

Affected men transmit the disease to all their daughters and none of their children

Women affected heterozygotes transmit the disease with a probability of 50% both to their female daughters, as to males

Women are affected twice as much as men, but the phenotypic expression is milder.
PATTERNS OF NON-CLASSICAL HERITAGEMytochondrial Presence
• Mitochondrial heritage
• Germinal mosaicism
• Uniparental Disomy
• Genomic Imprint
• Triplet expansion

MITOCHONDRIAL INHERITANCE:

Mitochondrial DNA is a circular molecule, which has 37 genes, has no introns and 100% of the DNA is a single copy, encodes two RNAr, 27 RNAs and 13 polypeptides that are part of the enzymes NADH dehydrogenase, cytochrome oxidase and ATP synthesize.
The diseases that are due to these mutations show a different pattern of inheritance due to the following three common characteristics of the mitochondria.
a) Replicative segregation.

It is the main characteristic and it is about the absence of controlled segregation that is observed during mitosis and meiosis of the 46 nuclear chromosomes. During cell division, the multiple copies of mtDNA of each mitochondrion present replication and random distribution among newly synthesized mitochondria. In turn, the mitochondria are also randomly distributed between the two daughter cells.
b) Homoplasmy and heteroplasmy.

Homoplasmy: is the situation in which a daughter cell can randomly receive mitochondria that have only a pure population of mtDNA or a population of mutated mtDNA.
Heteroplasmy: a situation in which a daughter cell can randomly receive a mixture of mitochondria with the mutation and others without them.
c) Maternal heritage

All the children of a homoplasmic woman for a mutation will inherit this mutation, however it will not be inherited by the children of the men who carry a similar mutation.
The heteroplasmic women for point mutations and duplications will transmit them to all their children, however the percentage of mutant mitochondria in the descendants and therefore the risk and severity can vary considerably is the percentage of mutant mitochondria existing in the mother and according to the random distribution of the small number of mitochondria by cells in the second bottle of the oocyte. In general heteroplasmic deletions are not transmitted by hereditary mechanism.
The percentage of mutant mitochondria in different tissues of heteroplasmic individuals for a mutation can vary in a very important way, which makes the disease manifest as a serious aspect in the members of a family with heteroplasmy specific to a mitochondrial mutation . Pleiotropism and variable expressivity are frequent in the affected relatives.
GONADAL OR GERMINAL MOSAICISM
It is due to a mutation present in a percentage of the cells of the gonads, explains the occurrence of more than one child affected by an autosomal dominant disease, when the parents have phenotype and normal genotype.
It consists of the presence of an individual or at least a tissue of two cell lines that are genetically different but that come from a single zygote.

UNIPARENTAL DISOMY
It is when a diploid organism presents a pair of homologous chromosomes from one of its progenitors
Heterodysomy If the individual inherits the two different homologous chromosomes from the same parent
Isodysomy If the individual inherits two copies of the same homologous chromosome from one of their parents.
MECHANISMS OF UNIPARENTAL DISOMIANCE PRODUCTION
A) Gamete complementation
B) Trisomy rescue

GENOMIC IMPRONTA

Mechanism by which the expression of the phenotype of the disease depends on whether the mutant allele has been inherited from the mother or from the father.
Prader Willi syndrome: Deletion of chromosome 15 paternal allele.
Deletion 15q11-q13 in Prader Willi syndrome
Hypotonia Facies peculiar. Obesity. Mental retardation Hypogonadism.
Angelman syndrome: Deletion of chromosome 15 meterno.
Hypotonia, convulsions, incoordination, unmotivated laughter, severe mental retardation.
ANTICIPATION. EXPANSION OF TRIPLETES
Fragile X Syndrome