Principles of genetic inheritance Flashcards
True or false: Disorders determined by a change in a gene on an autosome show X linked inheritance
and Disorders determined by a change in a gene on one of the X chromosomes shows the autosomal inheritance
False, autosomal inheritances are seen in autosomes and X linked inheritance is seen in X linked inheritance
How would you identify an autosomal dominant inheritance on a pedigree?
- Successive generations affected
- Males and females are equally affected
- Both males and females are able to transmit
- Male to male transmission is observed
List the 8 features of AD inheritance?
> Petentrance(percentage of individuals expressing the diseases to any degree)
- Some disease may show reduced or incomplete penetrance, misleading to a recessive
- Some show age-dependent penetrance
> Variable expressivity
- Variation in the severity of the disorder in individuals with the same disease
- There are interfamilial and intrafamilial expression
> Anticipation
*Worsening of the disease severity with successive generations, it occurs is in triplet repeat disorders
> Pleiotropy
*Manifestation of AD disease in different body systems in numerous ways
> New mutation rates
- The sudden unexpected appearance of an AD condition arising from a mutation occurring in the transmission of a gene
- Paternal age
> Somatic mosaicism
*New mutation arising in early embryogenesis resulting in more than 1 population of cells in an embryo
> Gonadal mosaicism
*A new mutation arising during
oogenesis or spermatogenesis this can result in couples having more than 1 child with a disorder due to more than 1 population of cells in the gonads
> Allelic heterogeneity
*Phenomenon in which different mutation at the same locus result in the same disorder
Discuss Neurofibromatosis ,how it can be identified (symptoms) and pathogenesis
*It was previously known as “von Recklinghausen disease “
> symptoms
- Cafe au lait macules (brown spots)
- Axillary and inguinal freckling
- Neurofibroma
- Iris lisch nodules
Mode of inheritance :
AD
Pathogenesis :
*heterogenous pathogenic variants in the NF1 gene on the chromosome 17q11.2
NF1 gene is considered a tumor suppressor gene. Because it is a large gene many mutations can occur .This gene encodes protein neurofibromin
What are the genetic principles of neurofibromatosis type 1?
- Autosomal dominant inheritance
- variable expressivity
- complete penetrance
- new mutation 50%
- allelic heterogeneity
- pleiotropy
How can an autosomal recessive inheritance be identified on a pedigree?
- Does not occur in every generation (trait can skip a generation )
- Males and females are equally affected
- Both males and females can transmit the disease( always inquire about consanguinity when dealing with autosomal recessive diseases )
Autosomal recessive conditions characteristics
- Most are born healthy to parents that are carriers
- often there are no affected individuals in the previous generation
- sibling risk to be carriers is 2/3
- precise risk for the general population depends on the frequency of carriers in the population
- Risk of AR disorder increases if it is a common condition or there is consanguinity
What are the common AR conditions
- cystic fibrosis
- spinal muscular atrophy
- oculocutaneous albinism
List the 4 concepts of AR inheritance?
> Compound heterozygotes: Presence of more than 1 different mutations at the same locus, constituting allelic heterozygosity
> Double heterozygosity
*The presence of 2 different mutated alleles at two separate loci eg sensorineural hearing impairment
*families described in which all the children born to parents who have hearing impairment due to AR have normal hearing
What is the difference between OCA 1 and OCA 2?
> OCA 1 is common among caucasian patients while OCA 2 is common among black South Africans
> OCA1 caused by pathogenic mutations in the Tyrosine gene on chromosome 11q14 whereas OCA2 is due to mutations in the OCA2 gene(15q12) which encodes a transmembrane P-protein found on the melanosomal membrane
> OCA1 results in the Deficiency of the enzyme tyrosine, which is necessary to form melanin from tyrosine whereas in OCA2 the most common mutation is deletion.
> The ultimate results of both OCA 1 and 2 is lack of melanin pigment in skin,hair,iris, eyes
What is the difference between X-linked and autosomal inheritance?
genes located on the X and Y chromosome are unequally distributed
T/F: 900 protein-coding genes have been identified on the x chromosome and 100 have been linked with X linked diseases
false; 800 protein-coding genes have been identified on the X chromosome and more than 300 are known to be associated with X linked diseases
A male with a mutant allele at X linked locus is – for that allele
hemizygous
Explain the process of X chromosome inactivation
This process is under the control of the X-inactivation center located at Xq13.3 and contains the XIST gene . The gene produces a non-coding RNA that spreads an inactivation methylation signal up and down the X chromosome on which is located
What is the clinical relevance when it comes to X linked genetic disorders
*Females may show mild/full expression of an X linked disease if .50% of the normal X chromosome are inactivated
this is known as Skewed X - inactivation
