Genetic &

Developmental Disorders

By: Jenna M. Filipone

Lesson Objectives... Understand what are the following: human cell,

chromosomes, and genes. Explain the errors that can occur in Meiosis and

Mitosis Explain the differences between autosomal

recessive, autosomal dominant, and X-Linked genetic disorders.

Understand inheritance patterns in single-gene disorders which are seen through geno-imprinting, anticipation, and mitochondrial inheritance

Understand that environmental issues can also cause issues with development

What is a Genetic Disorder?

Disease cause by an error in an individuals DNA during fetal development › These errors include…

Errors in Cell Division Errors in Chromosome Division Adding or deleting Chromosomes Mutations within Gene’s or a Single

Gene

Genetic Disorders…The Cell Two Key Parts: Nucleus and Cytoplasm

› Nucleus Chromosome & DNA organized into Gene’s needed for

life › Cytoplasm

Gene in the nucleus are dependent on the cytoplasm

› The Nucleus and Cytoplasm need to be working in unison so that there are NO defects in Gene Development

› If an error occurs an any phase during development it opens a wide range of genetic disorders

Cell Division Two Types of Cell Division

› Mitosis (Non-reductive Division) Two Daughter Cells (46 chromosomes each)

formed from one parent cell › Meiosis (Reductive Division)

Four Daughter Cells (23 chromosomes each) are formed from one parent cell Only Seen in Germ Cells (Cells creating Sperm &

Egg) › Differences in Mitosis & Meiosis

Different in the 1st phase of cell division – Crossing over of Genes which can cause disorders but very rare Prevents the chances of having “clones” as siblings

Cell Errors: Chromosomes

Division Errors: Nondisjunction› 1 sperm or Egg gets 22 or 24 chromosomes

not the required 23 › Error causes defects like…Down Syndrome

or Turners Syndrome Children will suffer from intellectual delays,

unusual facial features, congenital malformations

Occurrence: 6-9/1000 live births 95% of individuals with Down Syndrome

develop this way

Types of Errors in Chromosomes Chromosomal Loss

› Turners Syndrome: 45 Chromosomes – Missing a X or Y › 99% miscarriage rate › Features include.. Webbed neck, nonfunctional ovaries,

poor development of the cardiac muscle Unlike Down Syndrome – No real delay in intelligence

Mosaicism› Loss of extra chromosome › Very rare and seen only in 5-10% of Chromosomal

abnormalities Translocation

› Transfer of 1 chromosome to a completely different 1 › Results in Down Syndrome because of extra

chromosome (Trisomy 21)

Types of Errors in Chromosomes Cont. Deletion

› Part if not all chromosome is lost 1 in 50,000 Causes: Unusual Facial features with round

face, wide spread eyes, lower set ears, intellectual disabilities

› Williams Syndrome of Micro-deletion Causes: Intellectual Disabilities, distinctive

facial features, heart defects› YCFS

Causes: cleft palate, heart defects, characteristic facial features, learning disabilities

Gene’s and their Functions Function of Gene

› Produce proteins and to regulate the function and development of the body

› Composed of DNA (Double Helix) A-T and C-G meet up to make gene combinations

› Over 3.3 Gene combinations

Genes can turn on and off

Errors occurs when the body does not properly turn gene’s on and off.

Gene Errors and Disorders Errors caused by…

› Transcription› Translation› Mutations

Point Mutations Insertion and Deletions Triple Repeat Disorder

Gene Disorders…› Selective Advantage› Single Nucleotide Polymorphisms (SNPs)› Single Gene (Mendelian) Disorders

Autosomal Recessive Disorders Autosomal Dominant Disorders X Linked Disorders

Transcription & Translation

TRANSCRIPTION:› Rarely see any errors during this process › DNA unzipping allowing mRNA to make a

copy of information› Errors are prevented because of “Proof

Reading” enzyme

TRANSLATION:› mRNA travels from nucleus to cytoplasm to

create protein

Gene Mutations Point Mutations

Most common type caused by single based pair substitution

› Missense Mutation : change in triple pair causing the wrong amino acid to attach in a protein chain

› Nonsense Mutation: Termination of Protein

Gene Mutations Cont. Insertion and Deletion:

› Most common Insertion: Polio› Most common Deletion: Duchenne

Muscular Dystrophy › Frame Shift: Tay-Sachs Disease

Triplet Repeat Expansion:› Over production of codons causing genes to

turn off› Causes: Huntington Disease and Fragile X

Syndrome

Selective Advantage Incidence in genetic diseases depends

on the amount of mutations that occur and the amount that are removed

National selection helps eliminate these problem genes› Sickle Cell Anemia

Single Gene (Mendelian) Disorders Autosomal Recessive

Disorders › Incidents are very rare › 1700 disorders- inherited

from mother and father› EXAMPLE: Tay-Sachs

which is when the body is unable to properly break down nerve cells causing a build up of toxins in the brain

Single Gene (Mendelian) Disorders Autosomal Dominate

Disorders › 4500 autosomal

disordered identified › 1 in 500 live births › Single abnormal allele› Example:

Achondroplasia and Neurofibromatosis

Single Gene (Mendelian) Disorders

X-Linked Disorders› Mutation in the sex

chromosome (X chromosome) › 900 X-Linked Disorders› 25% of males and 10% of

females with intellectual/learning disabilities are affected by X-Link Disorder

› Example: Duchenne Muscular Disorder

Mutation in the muscle cell membrane

Fragile X-Syndrome Most common X-Link Disorder

Revising Mendelian Genetics Genomic Imprinting Traits are inherited from the mother and father but there is a gene deletion that occurs from either the mother or the father. - Prader-Willi Syndrome which is characterized by short statue, obesity, and intellectual disabilities.

- Angelman Syndrome which is characterized by intellectual disabilities and epilepsy.

**Reasons for genomic imprinting is remains unclear

Revising Mendelian Genetics Anticipation› Abnormal gene manifest increasing the

severity of the disease or disorder with each generation.

› Example: Huntington Disease Caused by a triple repeat in gene formation. Autosomal dominant progressive neurological

disease which is associated with movement and cognitive disorders and impairments which increases with each generation

Revising Mendelian Genetics Mitochondrial inheritance › The genes with-in the DNA can mutate

causing the mitochondria to not perform efficiently causing deficient energy production and disease. EXAMPLE: MELAS which stands for

Mitochondrial encephalomymelopathy lactic acid and stroke like episodes. It is carried on by the female gene only An unaffected mother is able to pass the

deficient gene on to her children both male and female. Males can be effected but they can not be carriers.

Environmental Influences - The environment can affect the

phenotype of an individuals gene’s. - Environmental factors can effect the ways at which gene’s are expressed. - EXAMPLE: 2nd generation Asians growing up in the U.S. are taller than their parents due to an increase in protein intake during adolescence

- Disorders like diabetes, meningomyelocele, cleft palate, pyloric stenosis are affected by both the genotype and phenotype factures.

Summary Humans have 46 complementary genetic

chromosomes which determine our physical appearance and biological makeup but effect what we pass on to our offspring.

When genes mutate, split incorrectly, delete or add chromosomes it can have a lasting effect on the outcome of a persons offspring

Many problems can occur during pregnancy however even with all the issues that can occur, 95% of infants are born with out defects.

REVIEW What is a human cell? Chromosome? Gene?

What errors can occur in Meiosis and Mitosis?

What are the differences between autosomal recessive, autosomal dominant, and X-Linked genetic disorders?

What are the inheritance patterns in single-gene disorders (geno-imprinting, anticipation, and mitochondrial inheritance)?

What environmental factors can also cause issues with development ?

FYI… Interesting Info

Females have over 2 million Eggs Trisomy is the common cause of miscarriages Human genome contains 20,000-25,000 genes. Fruit

Fly contains 13,000 and a Round Worm contains 19,000

Chimps share 99% of your human genome People of all races and geography share 99.9% of the

same genetic identity There is only 1% that we do not share. (SNP’s)

Many problems can occur during pregnancy however even with all the issues that can occur, 95% of infants are born with out defects.

References Batshaw, M. L., Pellegrino, L., Roizen, N.J. (2007). Children with Disabilities (6th ed., pp 3-20). Baltimore, MD: Paul H Brooks  U.S. National Library of Medicine. (2012, July 9). Genetics Home Reference: Your Guide to Understanding Genetic Conditions. Autosomal Recessive. Retrieved July 12, 2012 from http://www.beyondbatten.org/about- prevention.html

Mayo Clinic Foundation for Medical Education and Research. (2012, May 24). Autosomal Dominate Inheritance Pattern. Retrieved July 11, 2012 from http://www.mayoclinic. com/health/m edical/IM00991

Mayo Clinic Foundation for Medical Education and Research. (2012, May 24). Muscular Dystrophy X-Linked Recessive Inheritance Pattern with Carrier Mother. Retrieved July 11, 2012 from http://www.mayoclinic.com/health/medical/IM02723