Multifactorial Inheritance & Genomic Imprinting

What percentage of human genetic diseases are caused by monogenic diseases?

represent only a small portion of the total burden of human genetic disease.

What causes multifactorial diseases?

result of a complex interplay of multiple genetic and environmental factors.

Who observed "blending" characters in 1897?

Francis Galton observed "blending" characters in 1897.

What is referred by blending characters?

intermediate expression blend of genetic influences from both parents

What is a characteristic of multifactorial diseases in terms of phenotype expression?

multifactorial diseases show a gradation in the expression of the phenotype. either mild or severe

What does "multifactorial" refer to in genetics?

traits where each genotype confers a different phenotype.

What type of traits are often multifactorial?

Many quantitative traits are multifactorial.

What is the polygenic inheritance?

involves many genes influencing a trait

What is oligogenic inheritance?

involves a few genes influencing the trait.

How can multifactorial diseases occur in terms of family history?

can occur in isolation, but familial aggregation is common.

When do multifactorial diseases typically manifest?

late onset.

How do environmental influences affect multifactorial diseases?

can increase or decrease the risk of multifactorial diseases

Do multifactorial diseases show a gender preference?

occur more frequently in one gender than the other, but they are not sex-limited traits meaning both gender can still be affected

How does the risk of a multifactorial disease differ among family members?

First-degree relatives (parents, children, sibilings) have a higher risk of developing a multifactorial disease.

Are there certain populations more affected by multifactorial diseases?

Yes disease can occur more frequently in specific ethnic groups bc of environmental factors and genetics

e.g. CVD higher in Latin America → HTN greater risk than Asian Americans

Can some single-gene disorders show additional variation?

present additional variation caused by environmental or genetic factors.

What is the difference between monogenic and multifactorial diseases in terms of mutations?

Monogenic diseases involve mutations with a big effect,

multifactorial diseases involve mutations in different genes with a small effect.

What are some key differences between multifactorial and monogenic diseases?

Multifactorial diseases show locus heterogeneity, variable expression, and incomplete penetrance, while monogenic diseases typically do not.

What is locus heterogeneity?

different genes can cause similar diseases

What is variable expression?

even with same gene mutation, ppl experience the disease in different ways different severity.

How does the penetrance of a gene affect environmental impact?

greater the penetrance of a gene, the lower the environmental impact on the disease.

What is heritability?

refers to the proportion of variation in a trait that can be attributed to genetic factors.

How does the number of affected family members influence recurrence risk in multifactorial diseases?

recurrence risk is higher if more than one family member is affected.

How does the severity of the disease in the proband affect recurrence risk?

If the expression of the disease in the proband is more severe, the recurrence risk is higher.

How does the sex of the proband affect the recurrence risk in multifactorial diseases?

The recurrence risk is higher if the proband is of the less commonly affected sex.

How does the relationship of relatives to the proband affect recurrence risk?

The recurrence risk for the disease usually decreases rapidly in more remotely related relatives.

How can family pedigrees help study multifactorial diseases?

can help trace the inheritance patterns and recurrence risks of multifactorial diseases within families.

What role do twin studies play in studying multifactorial diseases?

help compare the frequency of traits between monozygotic (identical) and dizygotic (fraternal) twins to understand the genetic and environmental contributions to multifactorial diseases.

What is the difference between monozygotic and dizygotic twins in studying multifactorial diseases?

Monozygotic twins share 100% of their genetic material, while dizygotic twins share 50%, helping researchers assess the influence of genetics versus environment.

What does it mean if both members of a twin pair share a trait?

concordant.

What does it mean if members of a twin pair do not share a trait?

they are said to be discordant.

What is the role of GWAS (Genome-Wide Association Studies) in studying multifactorial diseases?

identify susceptibility loci by analyzing genetic variations across the genome to determine their association with multifactorial diseases.

What are examples of multifactorial diseases?

Diabetes

HBP

Obesity

Cancer

Esphinophilia peptic ulcer

Cleft lip

aretheriosclerosis

alzheimer

asthma

What is genomic imprinting?

process where one of the alleles of a gene is transcriptionally inactive depending on the parent from whom the allele was inherited

How many transcriptionally active copies of a gene does a normal individual have in genomic imprinting?

would have only one transcriptionally active copy of the gene.

What does genomic imprinting involve in terms of gene expression?

involves the silencing of one allele of the gene, depending on the parent of origin.

How many human genes are known to be imprinted?

At least 100 human genes are known to be imprinted.

What is genomic imprinting?

epigenetic phenomenon that causes genes to be expressed in a parent-of-origin-specific manner.

What are some epigenetic processes involved in genomic imprinting?

methylation, acetylation, and condensation of chromatin, which inhibit transcription.

Where are the epigenetic marks for genomic imprinting established?

in the germline (sperm or egg cells) of the parents.

How are epigenetic marks for genomic imprinting maintained?

through mitotic cell divisions in the somatic cells of an organism.

What chromosomal region is affected in Prader-Willi and Angelman syndromes?

4 Mb region of the long arm of chromosome 15.

What type of genes are located in the affected region of chromosome 15?

Imprinted genes.

What transcript is associated with Prader-Willi syndrome?

SNURF-SNRPN.

How does genomic imprinting normally affect chromosome 15?

maternal chromosome is normally imprinted (silenced), while the paternal chromosome is active.

What causes Prader-Willi syndrome?

the paternal chromosome 15 is imprinted (silenced) or

if the individual inherits two copies of chromosome 15 from the mother.

What is the normal imprinting pattern of chromosome 15 related to Angelman syndrome?

the father's chromosome 15 is imprinted (silenced), while the mother's is active.

What causes Angelman syndrome?

occurs when the maternal chromosome 15 is imprinted (silenced) or when an individual inherits two copies of chromosome 15 from the father.

How common are Prader-Willi and Angelman syndromes?

Both occur in about 1 in 15,000 individuals.

What is the most common genetic cause of Prader-Willi and Angelman syndromes?

Chromosome deletions account for about 70% of cases of both diseases.

What are common symptoms of Prader-Willi syndromes?

Hypotonia, delay in psychomotor development, intellectual disability, and behavioral problems.

What hormonal deficiency is associated with Prader-Willi syndrome?

in the production of hormones from the hypothalamic-pituitary-adrenal axis.

What metabolic issues are common in Prader-Willi syndrome?

Obesity, excessive appetite, and a tendency to develop diabetes.

Breathing disorders while sleeping and sleep disturbances.

What system is primarily affected in Angelman syndrome?

The nervous system.

What are the main developmental symptoms of Angelman syndrome?

Delayed psychomotor development and poor motor coordination.

What neurological symptoms are associated with Angelman syndrome?

Epilepsy, ataxia (balance and movement problems), and difficulty with attention.

How does Angelman syndrome affect communication?

It leads to reduced or no linguistic capacity and poor communicative receptivity.

What are common behavioral traits of individuals with Angelman syndrome?

Hyperactivity, excitability, and an apparent state of permanent joy with frequent laughter and smiles.

What type of condition is Beckwith-Wiedemann Syndrome?

An overgrowth condition accompanied by an increased predisposition to cancer

What are common physical features of Beckwith-Wiedemann Syndrome?

Large size for gestational age, neonatal hypoglycemia, large tongue, ear lobe creases, and omphalocele.

Which gene is involved in Beckwith-Wiedemann Syndrome?

IGF2, which is normally inactive on the maternal chromosome.

What genetic mechanisms contribute to Beckwith-Wiedemann Syndrome?

Paternal uniparental disomy and loss of imprinting on the maternal copy.

How does gene expression change in Beckwith-Wiedemann Syndrome?

There is an overexpression of IGF2 due to loss of imprinting.

What are the key characteristics of Silver-Russell Syndrome?

Growth retardation, proportionate short stature, leg length discrepancy, and a small triangular-shaped face.

What genetic factor is downregulated in Silver-Russell Syndrome?

IGF2 (Insulin-like Growth Factor 2).

What type of imprinting defect occurs in Silver-Russell Syndrome?

Imprinting defects of the paternal chromosome.

What type of uniparental disomy is associated with Silver-Russell Syndrome?

Maternal uniparental disomy.

What type of mutation affects IGF2 in Silver-Russell Syndrome?

Loss-of-function mutations.