Genetics

Definition

Gene & Allele

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.

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.

Function

Genes tell the body how to make specific proteins. There are approximately 20,000 genes in each cell of the human body. Together they make up the hereditary material for the human body and the way it functions. The genetic makeup of a person is called the genotype.

Gene balance

Genetic balance is the condition of an allele or genotype in a group of genes (such as a population) where the frequency does not change from generation to generation. Genetic equilibrium describes a theoretical state that is the basis for determining if and how populations can drift.

Genetic Analysis of Single Genes

Mendel’s First Law

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.

Sex-linked pattern of inheritance

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.

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.

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.

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Environmental Factors^

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.

Penetrance and Expressivity

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

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.

Gene Variation

Polymorphisms

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^

Mutations

Origin

are changes in DNA sequences

Types

mutations of biological origin ^

incorrect bases can be incorporated during DNA replication, if these are not repaired and remain in the daughter strand they will cause a mutation.

During DNA replication, strand delamination can also occur, causing the bases to shift and not be paired with the opposite strand.

If the loop forms on the template strand, the bases will not replicate and a loss will occur on the growing daughter strand.

if the child string is looped, it can replicate again causing an insertion of an additional sequence in the string.

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 l: transposed by an RNA intermediary, they are reverse transcribed into DNA by enzymes such as integrase.

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.

amorphous alleles

have complete loss of function, do not make any active principle and lack of transcription, they can be called null alleles.

hypomorphic alleles

have a partial loss of function, make an incompletely functioning product and concentrate as leaky mutations.

hypermorphic alleles

produce more of the same active ingredient and is due to increased transcription.

neoform alleles

produce an active product with new function

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.

Mode of inheritance

Autosomal Dominant (AD)

general characteristics

expressed in heterozygotes

vertical transmission

occurs in both sexes

the affected individual has a 50% chance of inheriting the trait to his/her DESCENDANT, if crossed with a healthy individual.

If two affected individuals are crossed, their offspring will have 75% of being affected and 25% of not having the mutant allele.

X-linked dominant (XD)

general characteristics

affected men with normal partners do not have affected sons or normal daughters.

the frequency of affected females is twice that of males, but females have a mild expression of the phenotype.

sons and daughters of carriers have a 50% chance of inheriting the phenotype

Autosomal recessive (AR)

general characteristics

manifests in recessive homozygotes

can skip generations

HETEROCIGOTIC parents have 25% of affecting their OFFspring.

the frequency of these diseases increases if there is CONSANGUINITY or inbreeding.

general characteristics

Any male who inherits an X-linked recessive allele will be affected by it since males have only one X chromosome.

expressed phenotypically in all individuals.
male who possess it. Furthermore, individuals
females express it when they are homozygous
for the mutation.

general characteristics^

Two additional modes are Y-linked and mitochondrial inheritance.

Only men are affected by this type of inheritance, likewise, they can only inherit it from their children.

For example

An example of Y-linked inheritance is the shaggy earflap phenotype seen in some Indian families.

Mitochondrial DNA mutations are inherited through the maternal line (from your mother). There are some human diseases associated with mutations in the mitochondria genes.

These can affect both men and women, but men cannot pass them on since mitochondria are inherited through the egg, not the sperm.

are^

Many diseases that have a hereditary component have more complex patterns of inheritance due to (1) the involvement of multiple genes and/or (2) environmental factors.

diseases with similar symptoms can have different causes, some of which may be genetic and some of which may not

For example

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.

Subtopic

Hardy-Weinberg

is

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.

This is the basis of the Hardy-Weinberg formula:𝑝2+ 2 𝑝 𝑞+𝑞2= 1

genotypic frequencies, like allele frequencies in a population, remain unchanged after successive matings within a population, if certain conditions are met

The conditions are^

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.
^

No natural selection: all genotypes have the same fitness.

Non-migration: Individuals do not leave or enter the population.

No mutation: The allele frequencies do not change due to the mutation.

Large population – The effects of random sampling on mating (i.e., genetic drift) are negligible in large populations.

Mendel’s Second Law

Independent Assortment

is

Two loci are distributed independently of each other during gamete formation.

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.

Gene Interactions

We can find

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.

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.

characteristics

Recombination is defined as any process that results in gametes with a combination of alleles that were not present in the gametes of a previous generation.

alleles at loci that are close together on the same chromosome tend to be inherited together. This phenomenon is called binding, and it is a major exception to Mendel's second law of independent distribution.

Recombination frequencies tend to underestimate map distances, especially over long distances, as double crosses may be genetically indistinguishable from non-recombinants.

Measuring recombination frequency is easiest when starting with inbred lines with two alleles for each locus and with lines suitable for the test cross.

Genetic Mapping

Because the recombination frequency between two loci (up to 50%) is roughly proportional to the chromosomal distance between them, we can use recombination frequencies to produce genetic maps of all loci along a chromosome and ultimately , in the whole genome. Units of genetic distance are called map units (mu) or centiMorgans (cM).^

A genetic map shows the map distance, in cM, separating two loci and the position of these loci relative to all other mapped loci. Thus, they are useful for tracing genes/alleles in crop and animal husbandry, for studying evolutionary relationships between species, and for determining the causes and individual susceptibility of some human diseases.

Changes in Chromosome Number

Changes in Chromosome Structure

Cause 1 -Incorrect Repair of Double Strand DNA Breaks During Interphase

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.

The Four Types of Chromosome rearrangements

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.

Inversions

when both breaks are in one chromosome, it will be inverted.

paracentric: does not include the centromere

pericentric : includes the centromere

Duplications

can occur from two DNA strands, the ends of which are incorrectly joined giving a chromosome with a duplication.

Translocations

ruptures in different chormosomes

reciprocal translocation: exchanged arms

reciprocal translocation: exchanged arms

cause 2- Incorrect Crossovers During Meiosis

Chromosomal abnormalities in humans

The problems described above can affect all eukaryotes, unicellular and multicellular. The convention when describing a person's karyotype (chromosomal composition) is to list the total number of chromosomes, then the sex chromosomes, and then anything out of the ordinary. Most of us are 46,XX or 46,XY. What follows are some examples of abnormalities in chromosome number and chromosome structure.

This chapter discusses the following diseases

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.

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.

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.

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.

Diagnosing Human Chromosome Abnormalities^

bright field microscopy

This method simply involves taking a sample of your cells, staining the chromosomes with Giemsa stain, and examining the results under a light microscope.

fluorescent in situ hybridization

a single-stranded DNA probe is allowed to hybridize to the denatured target DNA.

Using FISH to Diagnose Down Syndrome

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.

Using FISH to Diagnose Cri-du-Chat Syndrome^

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.

newer techniques