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FISH can be used to confirm the diagnosis. For example, shows a positive result for cri-du-chat syndrome. The probes bind to two long arms of chromosome 5 but only one short arm. Therefore, one of the 5 chromosomes must be missing part of its short arm.
A woman can choose amniocentesis. In this test, some amniotic fluid is removed so the fetal cells it contains can be examined. Thus, it can show a positive result for trisomy-21.
a single-stranded DNA probe is allowed to hybridize to the denatured target DNA.
This method simply involves taking a sample of your cells, staining the chromosomes with Giemsa stain, and examining the results under a light microscope.
This chapter discusses the following diseases
Klinefelter's syndrome
There are four common sex chromosome aneuploidies: 47,XYY, 47,XXX, 45,X and 47,XXY. This last situation is known as Klinefelter syndrome. These people are male (because they have a Y chromosome). They have no health problems because the X chromosome inactivation system is independent of sex. In the embryonic nuclei, the X chromosomes are counted and all but one is inactivated.
Turner syndrome
Monosomy (2n-1) for autosomal chromosomes occurs at conception, but these embryos almost never survive to term. Similarly, embryos that are 45,Y are also not viable because they lack many essential genes found on the X chromosome. The only viable monosomy in humans is 45,X, also known as Turner syndrome . These individuals are phenotypically female because they do not have a Y chromosome.
XYY y XXX
While trisomic fetuses for one of the other larger autosomes rarely survive to term, the situation is quite different for the sex chromosomes. About 1 in 1000 males has an extra Y chromosome and yet most don't know it! There is little harm in having two Y chromosomes because they have relatively few genes. Similarly, 1 in 1000 females has an extra X chromosome.
Down Syndrome
The most common chromosomal abnormality is trisomy 21 or, as it is more commonly known, Down syndrome . Having an extra copy of the smallest human chromosome, chromosome 21, causes significant health problems. It is present in about 1 in 800 births. Babies with this condition have three copies of chromosome 21 instead of the normal two.
Translocations
ruptures in different chormosomes
reciprocal translocation: exchanged arms
Duplications
can occur from two DNA strands, the ends of which are incorrectly joined giving a chromosome with a duplication.
Inversions
when both breaks are in one chromosome, it will be inverted.
pericentric : includes the centromere
paracentric: does not include the centromere
Deletions
when both breaks are in one chromosome, if they are joined in this way the piece of dna will not have a centromere and will lose in cell division.
When two strands break at or near the same place, this break will split the chromosome into two independent pieces, this will normally be corrected by the non-homologous end joining system.
if there is a double strand break the ends can recognize each other and join, but if there are two breaks at the same time there will be four broken ends.
dominant epistasis
In some cases, a dominant allele at one locus can mask the phenotype at a second locus. This is called dominant epistasis, which produces a segregation ratio such as 12:3:1, which can be seen as a modification of the 9:3:3:1 ratio in which the A_B_ class is combined with one of the other genotypic classes.
recessive epistasis
Epistasis (meaning "to stand on") occurs when the phenotype at one locus masks or prevents the phenotype at another locus. Therefore, after a dihybrid cross, fewer than the four typical phenotypic classes will be observed with epistasis.
Tying is one of the most important reasons for the distortion of the expected proportions of the independent assortment. Linked genes are found close together on the same chromosome. This proximity alters the frequency of allele combinations in gametes.
Two loci are distributed independently of each other during gamete formation.
genotypic frequencies, like allele frequencies in a population, remain unchanged after successive matings within a population, if certain conditions are met
The conditions are
Large population – The effects of random sampling on mating (i.e., genetic drift) are negligible in large populations.
No mutation: The allele frequencies do not change due to the mutation.
Non-migration: Individuals do not leave or enter the population.
No natural selection: all genotypes have the same fitness.
Random mating – Individuals of all genotypes mate with equal frequency. Selective mating, in which certain genotypes preferentially mate with each other, is a type of non-random mating.
This is the basis of the Hardy-Weinberg formula:𝑝2+ 2 𝑝 𝑞+𝑞2= 1
The frequency of different alleles in a population can be determined from the frequency of the various phenotypes in the population. Thus, with the allele frequencies of a population, one can calculate the expected frequency of each genotype after random matings within the entire population.
Subtopic
ALS (amyotrophic lateral sclerosis); approximately 5-10% of cases are inherited with a pattern of AD, while most of the remaining cases appear to be sporadic, that is, not caused by a mutation inherited from a parent.
An example of Y-linked inheritance is the shaggy earflap phenotype seen in some Indian families.
the frequency of these diseases increases if there is CONSANGUINITY or inbreeding.
HETEROCIGOTIC parents have 25% of affecting their OFFspring.
can skip generations
manifests in recessive homozygotes
sons and daughters of carriers have a 50% chance of inheriting the phenotype
the frequency of affected females is twice that of males, but females have a mild expression of the phenotype.
affected men with normal partners do not have affected sons or normal daughters.
general characteristics
If two affected individuals are crossed, their offspring will have 75% of being affected and 25% of not having the mutant allele.
the affected individual has a 50% chance of inheriting the trait to his/her DESCENDANT, if crossed with a healthy individual.
occurs in both sexes
vertical transmission
expressed in heterozygotes
Genetic Screens
is a way to identify the functioning of mutant genes by inducing mutations in a large population. The mutations induced will be heterozygous and will be limited to single cells, germ lines and somatic lines are studied.
Types
neoform alleles
produce an active product with new function
hypermorphic alleles
produce more of the same active ingredient and is due to increased transcription.
hypomorphic alleles
have a partial loss of function, make an incompletely functioning product and concentrate as leaky mutations.
amorphous alleles
have complete loss of function, do not make any active principle and lack of transcription, they can be called null alleles.
mutations due to transposable elements
These are present in all organisms, they have the ability to be cut or copied in their original location and inserted into any region of the genome, interrupting the function and becoming a mutation.
there are two types
class ll: known as transposons, they do not use an RNA intermediate, they use an enzyme called transposase that cuts the DNA from its original location and then inserts the new fragment.
class l: transposed by an RNA intermediary, they are reverse transcribed into DNA by enzymes such as integrase.
mutations of biological origin
During DNA replication, strand delamination can also occur, causing the bases to shift and not be paired with the opposite strand.
if the child string is looped, it can replicate again causing an insertion of an additional sequence in the string.
If the loop forms on the template strand, the bases will not replicate and a loss will occur on the growing daughter strand.
incorrect bases can be incorporated during DNA replication, if these are not repaired and remain in the daughter strand they will cause a mutation.
Origin
are changes in DNA sequences
is a difference in DNA sequencing that can determine various characteristics in an individual, and polymorphism refers to the fact that one allele is no more abnormal or normal than the other.
For example
a DNA sequence that determines hair color
Expressivity: Refers to the difference in the way the signs and symptoms of a genetic condition present in a patient with that condition. It is a method of quantifying the variation in the expression of a phenotype in the individuals that present the genotype to which that phenotype is associated.
Penetrance: Genetic penetrance is the proportion of individuals (percentage) of a population that express the pathological phenotype, among all those that present a genotype carrying a mutated allele. is the ability of a genotype to manifest a phenotype
Environmental factors, in relation to genetics, refer to exposure to substances (such as pesticides or industrial waste) at home or at work, to behaviors (such as smoking or poor diet) that may increase a person's risk of developing a disease
A genetic predisposition (also known as genetic susceptibility) is a higher chance of developing a particular disease based on a person's genetic makeup. A genetic predisposition results from specific genetic variations that are often inherited from one parent.
Sex-linked diseases are passed from parent to child through one of the X or Y chromosomes. These are sex chromosomes. Dominant inheritance occurs when an abnormal gene from one parent causes the disease, even though the compatible gene from the other parent is normal.
Y-linked inheritance
It occurs when the mutated gene that causes the disorder is located on the Y chromosome, one of the two sex chromosomes in males (XY). Because only males have a Y chromosome, in Y-linked inheritance, a mutation can only be passed from parent to child.
X-linked genes
When a gene is present on the X chromosome but not on the Y chromosome, it is said to be X-linked. X-linked genes have different patterns of inheritance than genes on non-sex chromosomes (autosomes). That's because males and females have a different number of copies of these genes.
Law of EqualSegregation
Through careful study of inheritance patterns, Mendel recognized that a single trait could exist in different versions, or alleles, even within an individual plant or animal. This is the basis of Mendel's First Law, also called the Law of Equal Segregation, which states: during gamete formation, the two alleles at a genetic locus segregate from each other; each gamete has the same probability of containing any allele.
Gene: The gene is considered the basic unit of heredity. Genes are passed from parent to offspring and contain the information necessary to specify physical and biological traits.
Allele: An allele is one of two or more versions of a DNA sequence (a single base or a segment of bases) at a given genomic location. People inherit two alleles, one from each parent.
Stages
Replication
Meiosis
Meiosis II
Gamete Maturation
the sister chromatids that make up each chromosome separate and are distributed among the nuclei of the daughter cells. Between these two successive stages, there is no stage S . The maturation of the daughter cells will give rise to gametes.
Meiosis I
Reductional division
Process by which a single parent cell divides to produce two daughter cells. Each daughter cell receives a complete set of chromosomes from the parent cell. This process allows the body to grow and replace cells.
Cell division of germ cells
In meiosis, a germ cell, after having duplicated its DNA (that is, with two homologous copies of each chromosome, each one already made up of two chromatids), divides giving rise to two cells with a single copy of each chromosome with two chromatids, cells that in turn divide into two, giving rise to four.
Mitosis
Cytokinesis
It consists of the division of the cytoplasm, which is divided between the two daughter cells. In animal cells, a contractile ring formed between the two nuclei is formed by microfilaments of actin and myosin, which strangles the cell, forming an hourglass-shaped structure.
Telophase
The cell is considered to be in telophase when the chromatids have reached their corresponding poles. Then, the chromosomal fibers have completely disappeared and the nuclear envelope begins to form around each group of chromosomes, which begin to decoil. Once the nuclear envelope has been organized and the nucleoli revealed, as a consequence of the resumption of rRNA synthesis, karyokinesis is considered complete. The division of the cytoplasm or cytokinesis, in animal cells, consists of a strangulation of the cytoplasm in its equatorial region, between the two daughter nuclei, which sometimes persists for some time and finally disappears, giving rise to two cells.
Anaphase
It begins when the centromeres split longitudinally, allowing the sister chromatids to move toward opposite spindle poles. The kinetochore fibers shorten while the polar fibers lengthen, thus accentuating the separation between the spindle poles and, therefore, between the two sets of chromatids.
Metaphase
As a result of the interactions between the chromosome fibers and the kinetochores, all the centromeres lie in the central plane and the longitudinal axis of each chromosome is oriented perpendicular to the axis of the mitotic spindle, so that each kinetochore faces a different pole.
Prophase
It begins when the chromosomes become visible under the light microscope. During this period the degree of chromatin packing increases, so the chromosomes become shorter and thicker and the centromeres begin to become visible. Each of the chromosomes, due to its duplication in S phase, is made up of two identical chromatids, called sister chromatids.
Cell growth and division
During mitosis, a cell duplicates its entire contents, including its chromosomes, and divides to form two identical daughter cells. Because of the criticality of this process, the steps of mitosis are carefully controlled by several genes.
Prokaryotes vs Eukaryotes
Prokaryotes
In prokaryotes there is only one origin of replication and in this are the recognition sites for the binding of the DnaA protein. This protein is the initiator of replication. It is an ATP-binding protein and is responsible for opening the two DNA strands in OriC.
Eukaryotes
DNA replication is semiconservative. Each strand of the double helix functions as a template for the synthesis of a new complementary strand. Enzymes called DNA polymerases produce new DNA, these require a template and primer (primer), and synthesize DNA in the 5' to 3' direction.
Gap 2 (G2)
Because the DNA has just been duplicated, the cell has twice the amount of genetic material. During this phase the cell prepares for cell division, continues to grow and synthesize organelles.
DNA synthesis (S)
when the cell synthesizes one copy of all its DNA. Once the duplicated DNA is available and there is a full complement of genetic material, the cell enters the G2 phase.
Gap 1 (G1)
The G1 phase is the one in which the cell prepares to divide. To do so, it enters the S phase, which is when the cell synthesizes one copy of all of its DNA.
Non-dividing (G0)
In this phase the cell is "quiescent", that is, it is not dividing, so it is outside the cell cycle.
Levels of compaction
heterochromatin
Constitutive heterochromatin is permanently silenced and has a basically structural function, and is mainly associated with centromeric or telomeric regions, important for the protection of the ends of chromosomes and the separation of chromatids in mitosis.
Euchromatin.
The more compact structure allows gene regulatory proteins and RNA polymerase complexes to bind easily to the DNA sequence, thus allowing the start of transcription.
Endoreduplication
Endoreduplication is the occurrence of two or more successive rounds of chromosome replication without going through any intermediate mitotic period.
Polyploids
is an organism that contains more than two complete sets of chromosomes
Aneuploidy
It also refers to any number of chromosomes that is not an exact multiple of the haploid number (23). Also called dysploidy and heteroploidy.
karyotype
Humans have a karyotype made up of 23 pairs of chromosomes, of each pair, one of the chromosomes is inherited from our father and another from our mother.
Morphological features
They have a short and a long arm separated by a primary narrowing or constriction, called the centromere.
