Genetic

Test Guidelines
A short essay about the Lab Test, with useful information and tricks to face it! Hope will be useful

1PART

Alessandro Motta, UVVG Medicine in English, 2nd Year

A karyotype is an organized profile of a person's chromosomes. In a karyotype, chromosomes are arranged and numbered by size, from largest to smallest. This arrangement helps scientists quickly identify chromosomal alterations that may result in a genetic disorder. To make a karyotype, scientists take a picture of someone's chromosomes, cut them out and match them up using size, banding pattern and centromere position as guides, it is made by digitalization of the picture and arranged on special dedicated software. What we need to know? Some general infos about normal Human Karyotype When examining a karyotype, the geneticist looks at each individual chromo- some. Every chromosome has a typical size and shape; the location of the centromere and the length of the chromosome arms (the parts on either side of the centromere) are what define each chromosomes physical appearance:

p arm: The shorter of the two arms q arm: The longer arm

In some disorders, one of the chromosome arms is misplaced or missing. Therefore, geneticists often refer to the chromosome number along with the letters p or q to communicate which part of the chromosome is affected. (eg: Downs Sindrome: (47,XX,+21) Hence it is really important for discriminate a normal karyotype from a pathological one the chromosomes counting: Aneuploid refers to an imbalance in the number of chromosomes. Situations involving aneuploidy are often given the suffix -somy to communicate whether chromosomes are missing (monosomy) or extra (trisomy). Euploid (and the related term, polyploid) refers to the number of sets of 1

chromosomes an organism has. Thus, diploid tells you that the organism in question has two sets of chromosomes (often written as 2n, with n being the haploid number of chromosomes in the set); when an organism is euploid, its total number of chromosomes is an exact multiple of its haploid number (n).

*Just to rehearse on some cue point: humans have 46 total chromosomes (2n) in all cells except for sexual cells (sperm and ovum) that have haploid situation (1n). Autosomal chromosomes as in picture are listed from 1-22 and sexual chromosomes are named just X and Y.

Now, a normal count of a human being karyotype is 2n or 46 or 44+XY. In pathological conditions we have to understand if the variation on counting came up from an Aneuploidy or from a Polyploidy: ANEUPLOIDY: It usually causes drastic phenotypic effects because it leads to unbalanced gene dosage. 1. Nullisomy is the loss of both members of a homologous pair of chromosomes. It is represented as 2n 2, where n refers to the haploid number of chromosomes. Thus, among humans, who normally possess 2n = 46 chromosomes, a nullisomic zygote has 44 chromosomes. (Could means death for the organism) 2. Monosomy is the loss of a single chromosome, represented as 2n 1. A human monosomic zygote has 45 chromosomes. 3. Trisomy is the gain of a single chromosome, represented as 2n + 1. A human trisomic zygote has 47 chromosomes. The gain of a chromosome means that 2

there are three homologous copies of one chromosome. Down syndrome result from trisomy of chromosome 21. 4. Tetrasomy is the gain of two homologous chromosomes, represented as 2n + 2. A human tetrasomic zygote has 48 chromosomes. Tetrasomy is not the gain of any two extra chromosomes, but rather the gain of two homologous chromosomes; so there will be four homologous copies of a particular chromosome. POLYPLOIDY: Most eukaryotic organisms are diploid (2n) for most of their life cycles, possessing two sets of chromosomes. Occasionally, whole sets of chromosomes fail to separate in meiosis or mitosis, leading to polyploidy, the presence of more than two genomic sets of chromosomes. It is normal in plants; it is rare in humans and leads to dead of the fetus (spontaneous abortions). Now focusing on local chromosomes rearrangements that affect the final number of counting we can find: duplications, deletions, inversions, and translocations. Chromosome duplication is a mutation that doubles part of a chromosome. This has major effects on the phenotype, possibly by altering gene dosage. Segmental duplications are common within the human genome. A chromosomal deletion is a mutation in which a part of a chromosome is lost. This cause recessive genes on the homologous chromosome to be expressed and may cause imbalances in gene products. In an inversion, a segment of a chromosome is turned 180 degrees. Inversions cause breaks in some genes and may move others to new locations. When crossing over takes place within the inverted region, nonviable gametes are usually produced, resulting in a depression in observed recombination frequencies. In translocations, parts of chromosomes move to other, non-homologous chromosomes or to other regions of the same chromo- some. Translocations can affect the phenotype by causing genes to move to new locations, where they come under the influence of new regulatory sequences, or by breaking genes and disrupting their function.

By the way whats remarkable for tomorrow: Having an idea of a normal Karyotype layout Chromosomes counting in normal and pathologic conditions Describing a pathology after counting the chromosomes I hope this part will be useful even if I went a little further for completeness

2PART The study of Genetic Disease can be made by using pedigrees to appreciate human characteristic inheritance. There are a few symbols we all should take care to remember:

***Hence Im pretty sure she would care about some typical disease threes
So I reported them case by case, only those more important and with an example of pathology!

This first case is a typical Autosomal dominant trait picture:

A dominant trait or disorder is one thats expressed (or manifested) in anyone who inherits the gene for the trait. In human pedigrees, autosomal dominant traits have some typical characteristics: males and females are affected with equal frequency; the trait doesnt skip generations, if neither parent is affected, and usually no child is affected. Typical autosomal dominant disorders: achondroplasia, polydactyly, Marfan syndrome, Huntington disease. Autosomal recessive traits: disorder can skip one ore more generations; affected children are born to unaffected parents, and there are different cases: Both parents carriers: 25% child affected Just one parent carrier: no child affected, 50% will be carrier One parent carrier, other affected: all children carriers, 50% affected One parent affected: all children carriers, no affected.

Pathologies: Cystic fibrosis is an autosomal recessive disorder that causes severe lung problems in affected persons; Sickle cells disease.

X-linked recessive traits: Males are XY and therefore have only one copy of the X-chromosome; they dont have a second X to offset the expression of a mutant allele on the affected X. Thus, similar to autosomal dominant disorders, X-linked recessive disorders express the trait fully in males, even though not homozygous. Females rarely show X-linked recessive disorders because being homozygous for the disorder is very rare. In pedigrees, X-linked recessive disorders have the following characteristics: more males than females affected; skip one or more generations, trait is never passed from father to son.

Some pathology involved: Hemophilia, Duchenne muscular dystrophy, also X- linked recessive conditions can sometimes manifest in females due to skewed X- inactivation or monosomy X (Turner syndrome).

X-linked Dominant traits: Like autosomal dominant disorders, X-linked dominant traits dont skip gen- erations. Every person inheriting the allele expresses the disorder. Affected mothers have both affected sons and daughters; all daughters of affected fathers are affected.

Diseases: Some X-linked dominant conditions, such as Rett syndrome, incontinentia pigmenti type 2 and Aicardi syndrome, are usually fatal in males either in utero or shortly after birth; exceptions to this finding are extremely rare cases in which boys with Klinefelter syndrome (47,XXY) also inherit an X-linked dominant condition and exhibit symptoms more similar to those of a female in terms of disease severity. Y-linked Dominant traits: the Y-chromosome is passed strictly from father to son. By definition, Y- chromosome traits are considered hemizygous, meaning theres only one copy of the chromosome, not two. Does not skip generations. Examples are male infertility and hypertrichosis pinnae.