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Pedigree analysis


Basics

to Pedigree analysis A geneticist always comes up when the desire to have children occurs in a family, but hereditary diseases have increased in the past. With a genetic pedigree it is possible to estimate and possibly limit the risks. But first of all a lot of basic knowledge:
Humans have a total of 46 chromosomes. By fertilizing egg and sperm cells, two haploid (2 x 23) chromosome strains of the mother and father become a diploid set of chromosomes (46). Accordingly, in each cell, apart from the germ cells, each chromosome is present in two variants. Once by the mother, and once by the father. One speaks also of homologous chromosomes (Chromosome pairs 1 to 22) because they carry the same genes. An exception to this are the sex chromosomes (chromosome pair 23), also under the technical term of heterologous chromosomes (Chromosome pair 23rd) known. You determine if we are genetically male (XY) or female (XX).
Whether certain hereditary diseases are expressed or not depends on the stored gene information on the individual chromosomes. How and what leads to the individual expression will become clear during the course of this learning module.
The pedigree analysis is essentially about two questions:
1. Is the characteristic to be examined (ie hereditary disease) over the autosomes (Chromosome pairs 1 to 22) or the Gonosomen (Sex chromosomes XX or XY) inherited?
2. Is one dominant- or a recessive Inheritance before? In dominant genomes, one dominant allele (either from the mother or father) is enough to develop the disease (Aa or AA). In the case of recessive inherited genes, on the other hand, both alleles must be identical (aa), so that it comes to feature development.
This results in five different combinations of inheritance, all of which are explained below with reference to an exemplary family tree.
Autosomal dominant inheritance
Autosomal recessive inheritance
X-linked dominant inheritance (gonosomal)
X-linked recessive inheritance (gonosomal)
Y-chromosomal inheritance (gonosomal)

Basic vocabulary and visualization

Biological vocabulary for precise expression is indispensable. Therefore at the beginning standard vocabulary from classical genetics:
Phдnotyp: external appearance of an organism. The appearance is always determined by the genotype. In the case of pedigree analysis, the phenotype is synonymous with the manifestation of the disease of the respective hereditary factor.
genotype: entire genetic make-up of an organism. For genealogical analysis, only two corresponding homologous chromosomes responsible for the development of the disease are considered for each mode of inheritance. In the case of autosomal inheritance, the variables A and a are used (representative of dominant and recessive), in gonosomal inheritance the variables X and Y (representative of the chromosomes) are used.
allele: refers to the different variants / expressions of a feature or gene
recessive trait: is displayed within the family tree analysis with the variable "a".
dominant feature: is displayed within the family tree analysis with the variable "A".
homozygous: both alleles are identical (either AA or aa)
heterozygous: both alleles are different (e.g., Aa)
Family trees are visualized uniformly:
circle (with color) = woman (with hereditary disease)
square (with color) = man (with hereditary disease)
Circle with dot = Conductor (transferee)

Autosomal dominant inheritance

For the expression of the trait in an autosomal dominant inheritance, at least one dominant allele (A) must appear in the genotype.
(1) and (2) are homozygous or heterozygous for the corresponding trait, so they are both ill. Their children (5) and (6) can only be characteristic bearers because of the mother (1). It always inherits at least one dominant allele, so that the genotype of the father does not matter.
On the other hand, the children of (3) and (4) can be quite healthy, since the mother (3) has two healthy alleles, and the father (4) has a healthy allele. As long as the dominant allele of the father (4) is left out, healthy children will always be homozygous (aa -> 7 & 9) and sick heterozygotes (Aa -> 8). Within an autosomal dominant inheritance, all healthy persons are genotypically always definable with (aa)! Consequently, the children of the parents (9) and (10) are invariably healthy, for if no parent possesses the trait, it can not be inherited.
In the descendants of (6) and (7), chance again decides whether or not they are characteristic carriers. Either the father (6) inherits the dominant gene or the recessive gene. In the first case the child is ill (11), in the second case homozygous healthy (12).
What indicates autosomal dominant inheritance?
Almost every generation has feature carriers
Women as well as men are affected in a similar ratio
If a child is positive for the trait, it is also a parent
Examples of autosomal dominant inheritance: Huntington's disease, Marfan's syndrome, neurofibromatosis, polydactyly (multiple finger)

Autosomal recessive inheritance

In order for a characteristic expression to occur in an autosomal recessive mode of inheritance, both recessive alleles must be homozygous (aa).
Mother (1) and father (2) are phenotypically healthy. However, they both carry the recessive (a) allele. Their offspring only become ill if they inherit the recessive gene from both parts of the elbow (6). As long as at least one dominant gene, either mother or father, is inherited, the child is phenotypically healthy (5).
In direct descendants of (3) and (4), hereditary disease will not occur without exception. Because the genotype of the mother (3) proves to be homozygous healthy, so that in the genotype of children always at least one (A) will be present.
Both the parents (6) and (7), as well as (8) and (9), the risk of further transmission. The probability for this is higher in (6) and (7), because mother (6), in contrast to father (8), will in any case pass on a recessive allele. In (8) there is still the possibility of a further transmission of the dominant allele (A).
What indicates autosomal recessive inheritance?
Not every generation has feature carriers
Women as well as men are affected in a similar ratio
Parents can be healthy while their children are characteristic
Examples of autosomal recessive inheritance: Albinism, cystic fibrosis, cretinism, sickle cell disease

X-linked dominant inheritance (gonosomal)

In contrast to autosomal inheritance, at gonosomal inheritance the traits are passed on to the sex chromosomes. Therefore, as variables, the chromosomes X (dominant), x (recessive), and Y (in this hereditary inheritance without meaning) are conveniently used directly.
Due to the fact that males have only one X chromosome, their genotype is always unique in X-linked dominant genomes. Either they have a recessive allele and are healthy (xY), or they have a dominant allele and are ill (XY).
The daughters of a father with characteristic expression will always form the disease phenotypically, because in each case they receive the dominant X chromosome. In the pedigree this is recognizable to father (7) and his daughters (10) and (11).
In the case of the heterozygous mother (1) and the healthy father (2), the randomness of the chromosome distribution once again determines whether or not the characteristic expression occurs (5 and 7) or not (6). Accordingly, even phenotypically healthy daughters are always genotypically determinable (xx).
Parents (3) and (4) on the other hand are insignificant for hereditary disease. As with autosomal dominant inheritance, non-inherited traits can not be inherited.
What indicates an X-gonosomal dominant inheritance?
In almost every generation there are characteristic carriers
Women like men are affected, the former usually more often
If the father is the characteristic bearer, so are all his daughters as well
Examples of X-gonosomal-dominant Erbgdnge: Alport syndrome, vitamin D-resistant rickets

X-linked recessive inheritance (gonosomal)

As with the X-linked dominant inheritance, men in X-linked recessive inheritance are always clearly identified in terms of their genotype and phenotype. Either they have a recessive allele and are ill (xY), or they have a dominant allele and are healthy (xy). Within this mode of inheritance, women function as leaders, therefore they transmit the recessive allele (x) without themselves being affected by hereditary disease (xx). In contrast to men, women can balance the recessive (diseased) gene with a dominant (healthy) gene, which does not lead to the expression of the trait. Therefore, significantly more men are affected in X-linked recessive inheritance.
In the present pedigree, (1), (3) and (6) are conductors of the hereditary disease. Chance decides again about the chromosomal distribution of offspring. Because of their dominant allele (regardless of the genotype of the father) both healthy (8) and sick (10,11) children are possible. There is only a difference in the probability of the characteristic being expressed, for a healthy father (7), in contrast to a sick father (4), inherits only dominant alleles (which prevent one expression).
But women can also get sick (9). Namely, when the mother is a conductor (3), and the father (4) is the carrier of hereditary disease.
What indicates an X-gonosomal-recessive inheritance?
For the most part, men are the characteristic carriers
Women as Conductors, without being affected
Women are affected only when father is affected and mother is a conductor
Examples of X-gonosomal-recessive Erbgdnge: Hemophilia (hemophilia), red-green-blindness

Y-linked dominant inheritance (gonosomal)

For the sake of completeness, mention should also be made of Y-linked dominant inheritance. As already noticed in the pedigree, only men are affected and that has a simple reason: women "lacks" the Y-chromosome. Therefore, there is only one single rule in trait inheritance in this mode of inheritance: Men always pass on the Y chromosome to their sons.
The Y chromosome is mainly responsible for the development of the male phenotype, but it has hardly any other genetic material itself, which is why the existence of this inheritance is by no means certain.
What indicates a Y-gonosomal dominant inheritance?
Only men are the characteristic carriers
If the father is affected, his sons are invariably too
Women are neither affected nor a conductor
Examples of Y-dominant-dominant genetic sequences: ?