Genetics and Genetic Diseases Overview

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Questions and Answers

What describes the likelihood that a genetic disease will manifest in offspring when one parent is unaffected and the other is heterozygous affected?

25% chance of disease in offspring

75% chance of disease in offspring

There is no chance of disease in offspring

50% chance of disease in offspring (correct)

Which characteristic is NOT associated with autosomal dominant inheritance?

50% transmission rate from affected parents

Rarity of affected individuals

Equal proportion in both sexes

Skipping generations is common (correct)

What is the term for the first diagnosed individual in a family with a genetic disease?

Propositive

Identical twin

Homozygote

Proband (correct)

Which statement accurately describes penetrance?

It represents the frequency of individuals expressing the expected phenotype Signup and view all the answers

In the case of age-dependent penetrance, which of the following conditions is known to manifest symptoms after a certain age?

Breast cancer Signup and view all the answers

Which factor can contribute to the occurrence of a new mutation leading to an autosomal dominant disease in a child with no prior family history of the disease?

A genetic change during gamete formation Signup and view all the answers

What role does the Y chromosome play in disease genetics compared to the X-linked genes?

Y chromosome predominantly affects male fertility while X-linked genes affect both sexes Signup and view all the answers

What percentage of individuals having a particular genotype will show the phenotype indicating complete penetrance?

100% Signup and view all the answers

What is the characteristic of obligate carriers in genetics?

They must carry the allele but do not express the disease. Signup and view all the answers

What is the typical male phenotype characterized by Klinefelter syndrome?

Short stature and gynecomastia Signup and view all the answers

Which statement about autosomal recessive diseases is true?

Individuals must be homozygous for a recessive allele to express the disease. Signup and view all the answers

How does consanguinity influence the prevalence of recessive diseases?

It increases the probability of offspring inheriting recessive alleles. Signup and view all the answers

Which term describes the different forms of a gene that can exist at a specific locus?

Alleles Signup and view all the answers

Which of the following is NOT a characteristic of Klinefelter syndrome?

Increased muscle mass Signup and view all the answers

What defines the genetic pattern seen in X-linked recessive diseases?

Females can be carriers without expressing the disease. Signup and view all the answers

In the context of autosomal recessive inheritance, what is the expected proportion of affected offspring from carrier parents?

1 in 4 Signup and view all the answers

What principle states that homologous genes separate during reproduction?

Principle of segregation Signup and view all the answers

In the context of genetic diseases, what does the term 'carrier' refer to?

An individual who has a disease-causing allele but is phenotypically normal Signup and view all the answers

What is a common lethal recessive disease that predominantly affects white children?

Cystic fibrosis Signup and view all the answers

Which of the following is NOT a characteristic of X-linked inheritance?

The Y chromosome is the primary carrier of relevant alleles. Signup and view all the answers

Which of the following modes of inheritance is characterized by traits that can skip generations?

Autosomal recessive Signup and view all the answers

What statement is true regarding the expression of autosomal recessive diseases?

The diseases show incomplete penetrance and variable expressivity. Signup and view all the answers

What describes the observable characteristics resulting from a combination of an individual's genotype and environmental influences?

Phenotype Signup and view all the answers

Which of the following is true regarding the incidence of Klinefelter syndrome?

Occurs in 1 in 1000 male births Signup and view all the answers

What is the inheritance pattern of X-linked recessive disorders in males?

Males only require one copy of the recessive allele to express the disease. Signup and view all the answers

Why are affected fathers unable to transmit X-linked recessive disorders to their sons?

The Y chromosome is the only chromosome passed from father to son. Signup and view all the answers

What does it mean if a trait is classified as sex-influenced?

It occurs more frequently in one sex compared to the other. Signup and view all the answers

Which condition is the most common and severe of all X-linked recessive disorders?

Duchenne muscular dystrophy Signup and view all the answers

What does the presence of the SRY gene on the Y chromosome indicate?

The initiation of gonadal differentiation begins. Signup and view all the answers

What can skipping generations in the inheritance of a genetic disorder indicate?

The disorder is X-linked recessive with carrier females. Signup and view all the answers

Which statement about precision medicine is true?

It uses individual genetic and environmental risk factors in diagnosis. Signup and view all the answers

How has the reduction in sequencing costs impacted genetic testing?

It allows for evaluation of entire germline DNA sequences for testing. Signup and view all the answers

Which enzyme's variance is known to influence the metabolism of many prescribed drugs?

CYP2D6 Signup and view all the answers

What characterizes triploidy in a zygote?

It contains three copies of each chromosome. Signup and view all the answers

What is the consequence of monosomy in a diploid cell?

It is always lethal. Signup and view all the answers

Which genetic disorder is associated with anomalies in the long arm of the X-chromosome?

Fragile X syndrome Signup and view all the answers

What type of structural abnormality involves losing a fragment of a chromosome?

Deletions Signup and view all the answers

What is a potential result of aneuploidy in cells?

Non-functional cells or syndromes. Signup and view all the answers

Which of the following conditions is characterized by a distinct facial appearance and congenital heart defects?

Down syndrome Signup and view all the answers

Which type of chromosome abnormality results from exchanges between non-homologous chromosomes?

Translocations Signup and view all the answers

What is the likely outcome for most triploid conceptions?

They are typically spontaneously aborted or stillborn. Signup and view all the answers

Which chromosomes characterize Turner syndrome?

A single X chromosome and no Y chromosome Signup and view all the answers

What common genetic condition is caused by nondisjunction during gamete formation?

Down syndrome Signup and view all the answers

What impacts the risk of having a child with Down syndrome?

Maternal age significantly. Signup and view all the answers

In which type of chromosomal abnormality is genetic material inverted?

Inversion Signup and view all the answers

What is the most significant genetic risk factor leading to Alzheimer's disease in Down syndrome individuals?

Duplication of chromosome 21. Signup and view all the answers

What is the typical chromosomal composition of somatic cells in humans?

23 pairs of chromosomes Signup and view all the answers

Study Notes

Genes and Genetic Diseases

Genes influence all aspects of body structure and function.
Defects in genes lead to recognizable genetic diseases.

Chromosomes

Two types of cells:
- Germline: mutations can be transmitted to the next generation.
- Somatic: diploid cells, 23 pairs of chromosomes.
Homologous chromosomes: 22 of the 23 pairs are virtually identical. The remaining pair (sex chromosomes) are X in females and X and Y in males.

Polyploidy

A germline or somatic cell has more than the diploid number of chromosomes (46).
Several types of body tissues (e.g., liver, bronchioles, epithelial tissue) are normally polyploid.
Triploidy: A zygote has three copies of each chromosome instead of the usual two.
Nearly all triploid conceptions are lost as spontaneous abortions or stillbirths.
Triploidy accounts for approximately 10% of known miscarriages.

Aneuploidy

Cells that do not contain a multiple of 23 chromosomes.
Monosomy: a diploid cell with only one copy of a given chromosome. Always lethal.
Trisomy: an aneuploid cell with three copies of one chromosome. Trisomy of chromosomes 13, 18, and 21 can sometimes survive.
Usually results from non-disjunction during meiosis or mitosis, where homologous chromosomes or sister chromatids fail to separate properly.

Abnormalities of Chromosome Structure

Parts of chromosomes can be lost, duplicated, or rearranged as gametes are formed.
Deletions: A gamete with a deletion uniting with a normal gamete results in a zygote with one chromosome having a normal complement of genes and one with missing genes.
Duplications usually have less serious consequences than deletions.
Inversions: the occurrence of two breaks on a chromosome followed by the reinsertion of the fragment at the original site, but in reverse order.
Balanced: no loss or gain of genetic material. Deletions and duplications can cause disease.
Translocations: interchanging of genetic material between non-homologous chromosomes
Robertsonian translocation: long arms of two non-homologous chromosomes fuse at the centromere, forming a single chromosome.
Reciprocal translocation: breaks in two different chromosomes and the material being exchanged.
Fragile sites:Areas of chromosomes that can develop microscopically observable breaks and gaps. Fragile X syndrome is a relevant example, located on the long arm of the X chromosome.

Down Syndrome

Most common example of aneuploidy chromosomal cells.
~10 cases per 800 live births.
Typically have low IQ quotients.
Risk increases with maternal age.
Approximately 97% caused by nondisjunction during gamete formation or early embryonic development.
Remaining 3% result from translocations.
Distinctive facial appearance (low nasal bridge, epicanthal folds, large protruding tongue, and flat low-set ears).
Congenital heart defects are common.
By age 40, often exhibit symptoms nearly identical to Alzheimer's disease; one of the Alzheimer's genes is located on chromosome 21.

Turner Syndrome

One of the most common single chromosome aberrations.
~1 in 2500 newborn females.
Presence of a single X chromosome; no homologous X or Y chromosome. Therefore, they are female but usually sterile.
Physical characteristics: short stature, webbing of the neck, widely spaced nipples, coarctation of the aorta (15-20% cases), edema of the feet in newborns, and sparse body hair.

Klinefelter Syndrome

Two X chromosomes and a Y chromosome.
Due to the presence of a Y chromosome, they have a male appearance. However, they are usually sterile.
Physical characteristics: 50% develop gynecomastia; testes are small; body hair is sparse; stature is elevated; and voice is somewhat high-pitched.
Moderate degree of mental impairment is often present.
~1 in 1000 male births.

Elements of Formal Genetics

Locus: location of a gene on a chromosome.
Alleles: Different forms of a gene at a particular locus. Alleles can determine differences between hemoglobin forms.
Polymorphic: When two or more alleles occur at appreciable frequencies in a population.
Genotype: genetic makeup at a given locus (compositions of genes).
Phenotype: the result of the genotype and environment.
Dominant allele: masks the effect of another allele in a heterozygote.
Recessive allele: will only be expressed in a homozygote.
Carrier: individual with a disease causing allele, but is phenotypically normal.

Transmission of Genetic Diseases

Pattern in which a disease is inherited across generations.
Mendelian traits: after Gregor Mendel.
- Segregation principle: homologous genes separate during reproduction & each cell only carries one gene of a homologous pair.
- Independent assortment principle: heritable factors are transmitted independently.
Four major modes of inheritance for known single-gene diseases : Autosomal dominant, Autosomal recessive, X-linked dominant, and X-linked recessive.

Pedigree Chart

Summarizes family relationships and the occurrence of genetic diseases.
Proband: Individual showing the disease. Also called propositus (male) or proposita (female).

Autosomal Dominant Inheritance

Both sexes exhibit the trait equally.
Does not skip generations.
Affected heterozygotes transmit the trait to approximately 50% of their children.
Two affected individuals can produce affected offspring together, although more common for affected heterozygotes to mate with a healthy individual.

Genetic Disease Characteristics

Recurrence risk: Chance a child will inherit a genetic disease. For one affected heterozygote parent and one healthy parent having a child, recurrence risk is 50%.
Each birth has an independent event; If there's no genetic history of disease in a family, the child's genetic disorder is likely a new mutation.

Genetic Disease Characteristics (continued)

Penetrance: The percentage of individuals with a particular genotype who also exhibit the expected phenotype, not all.
Incomplete penetrance: the individuals with a disease-causing allele may not exhibit the disease phenotype.
Age-dependent penetrance: Symptoms may not appear until later in a person's life
Obligate carrier: Individuals who have an affected parent and an affected child and must themselves carry the disease allele but do not have the disease themselves.
Examples of diseases: Breast cancer, colon cancer, hemochromatosis, and polycystic kidney disease.

Autosomal Recessive Inheritance

Rare diseases.
Individuals must be homozygous for recessive allele to express the disease.
Carriers are phenotypically normal; however they may have various expressivity and penetrance.
High frequency of carriers.
Common example: cystic fibrosis (~1 in 2500 births in a white population).
Defective Cl transporter leads to a salt imbalance and thick, dehydrated mucus secretions.

Autosomal Recessive Inheritance (continued)

Consanguinity (marriage between related individuals): a factor for producing recessive disease offspring.
Affected in equal proportions in males and females.
Usually affects siblings, not parents.
~¼ of the offspring of carrier parents will be affected.

X-linked Inheritance

Most sex-linked traits located on the X chromosome.
Females receive two X chromosomes and can be heterozygous, homozyous for the disease, or homozygous for the normal allele. Males receive one X chromosome and one Y chromosome.
Males who inherit a recessive disease allele on the X chromosome will be affected, since their Y chromosome will not have a gene to counteract it.
Males are more frequently affected in X-linked recessive diseases.

Characteristics of X-Linked Recessive Conditions

Seen more often in males than in females.
Females require two copies of the recessive allele to express the disease.
Males need only inherit one recessive allele from their mother.
X-linked recessive traits are never transmitted from father to son.
Affected fathers transmit to all daughters but they are usually carriers, not affected.
Approximately half of the sons will be affected.
Common example: Duchenne muscular dystrophy (DMD).

X-Linked Recurrence Risk

Most common is a carrier female mating with normal male.
The mother transmits the disease-causing allele to half of her offspring.
- Half the daughters will be carriers, and half will be normal.
- Half the sons will be normal and half will have the disease.

Sex Determination

Begins during the sixth week of gestation.
One Y chromosome is sufficient to initiate gonadal differentiation.
The number of X chromosomes doesn't alter this process.
SRY (Sex determining region on the Y): located on the short arm of the Y chromosome, acts as a trigger gene that initiates the action of genes involved in other chromosomes needed for male characteristics development.

Sex-Linked Traits

Sex-limited trait: Only occurs in one sex, often due to anatomic differences (i.e., breast development).
Sex-influenced trait: Occurs more frequently in one sex than the other, often due to the impact of hormones (i.e., male-pattern baldness).

Gene Identification

Precise gene localization on chromosomes.
Direct testing for disease-causing mutations is often not possible in most diseases.
Sequencing the whole human genome is becoming more affordable allowing for scanning for gene mutations that cause diseases in individual or family members.
Enables more accurate diagnoses.

Precision or Personalized Medicine

Taking into account unique genetic and environmental risk factors.
Diagnose disease by searching for disease-causing variances in patients entire DNA sequence.
Genetic testing to guide drug administration and dosage.
Variance in CYP2D6 gene, an example influencing drug metabolism in ~25% of prescribed drugs, through trial and error, reduce needed time for determining drug dosage requirements.

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Description

This quiz delves into the complexities of genes and genetic diseases, exploring their influence on body structure and function. It covers topics such as chromosomes, polyploidy, and aneuploidy, providing insight into how genetic defects can lead to various health issues. Test your understanding of these critical concepts in genetics.