BI 211 Genetics for Healthcare: Ch. 6 Autosomal Inheritance and Disorders

Autosomal inheritance

The inheritance patterns that occur when genes are located on autosomal chromosomes, not sex chromosomes

Chromosomes

large chunks of DNA with hundreds to thousands of genes

One set of chromosomes comes from _______, the other from ______.

mom, dad

These sets of chromosomes are split during..

meiosis

Autosomal chromosomes

1-22

Meiosis

cell division that produces reproductive cells in sexually reproducing organisms

Sister chromatids

Replicated forms of a chromosome joined together by the centromere

When are sister chromatids separated?

Meiosis II

How are the sister chromatids split in a normal Meiosis?

evenly between daughter cells

Homologous chromosomes vs. sister chromatids

Homologous chromosomes have have two similar chromosomes (one from mother one from father) while sister chromatids are an exact duplicate of the original chromatid

Crossing over

exchange of allele segments between non-sister homologous chromosomes

Chiasma

site of crossing over between homologous chromosomes

Recombinant DNA

DNA produced by combining DNA

When does crossing over occur?

Prophase I

Mistakes During Meiosis

Nondisjunction

Translocation

Nondisjunction

altered chromosome number in gametes or offspring due to an error in Meiosis I or II

Most nondisjunction errors are _______.

fatal

An abnormal number of chromosomes can cause what?

miscarriage

Translocation

pieces of chromosome exchanges between non-homologous chromosomes results in a free-standing chromosme being translocated onto another chromosome where it should not be

Since there are 2 cell divisions in Meiosis, how many opportunities are there for a nondisjunction event?

2

A nondisjunction event in Meiosis I will result in..

2 gametes with an extra chromosome

2 gametes with a missing chromosome

A nondisjunction event in Meiosis II will result in..

2 normal gametes

1 gamete with an extra chromosome

1 gamete missing a chromosome

Reciprocal translocation

pieces of non-homologous chromosomes switch places

Balanced translocation

when the same amount of DNA is present

Can translocations be seen in karyotypes?

YES

How do we indicate translocations?

t(first chromosome, second chromosome)

What else can be added if known?

if it occured on the p vs. q arm

Band numbers

Acrocentric chromosome

centromere is near the very top resulting in a very small p arm

Robertsonian translocation

two acrocentric chromosomes combine

Translocations are often....

balanced, meaning the total amount of genetic material is correct but it is just in a different location

Is gene expression often changed when genes move locations?

no

When do difficulties arise with translocation events?

gametogenesis

Trisomy

extra copy of a chromosome that is often fatal during fetal development

When are trisomies most common?

Advanced maternal age

Advanced maternal age

35 or older

Are any trisomy conditions survivable?

some

How do trisomies occur?

Gamete carrying translocation and the typical chromosome or nondisjunction during gametogenesis

Most common survivable trisomies

Trisomy 21

Trisomy 18

Trisomy 13

Sex chromosomes

Why are these chromosomes the most common survivable trisomies?

they are relatively small with gew genes and the X chromosome has barr bodies

Barr bodies

Inactivated X chromosomes in female cells

Extra chromosomes means..

extra genes

How is a trisomy indicated?

Number of chromosomes

Comma

Sex chromosomes

Plus sign

Trisomy chromosome number

Example of trisomy indication

47, XX, +21

Monosomy

one chromosome is lacking a pair

What is the one commonly seen survivable monosomy?

turner syndrome (1-22, X: sex-linked)

Trisomy 21

down syndrome

How rare is trisomy 21?

1:800 births with an equal race and ethnicity distribution

Common abnormalities for Trisomy 21

Single Palmar Crease

Epicanthal fold

Flat face

Wide eyes

Low ears

Short nose

Protruding tongue

Short neck

Common Phenotypes for Trisomy 21

Sleep apnea

Heart defects

Delayed intellect

Hypothyroidism

Poor muscle tone and sucking reflex

Cataracts

Low functioning immune system with increased infection risk

Intellectual delays depend heavily on?

environmental and educational stimulation

Hypothyroidism

lead to obesity and other issues

Life expectancy of Trisomy 21

increased dramatically, now 50-60 years

Reproduction for Trisomy 21

Males are sterile but puberty still occurs

Female can have normal reproduction but offspring have high likelihood of inheriting trisomy 21

Trisomy 18

Edward syndrome

Edward syndrome

Most individuals are stillborn and 90% die in the first year, females slightly more likely to survive

Common appearance of Edward syndrome

Small strawberry head with receding shin

Single palmar crease with clenched fists

Rocker bottom feet

Common Phenotypes of Trisomy 18

Seriously reduced intellectual development, heart and kidney defects, hernias, omphalocele and brain cysts

Life expectancy for trisomy 18

if not stillborn, days to months

Reproduction for trisomy 18

none

Trisomy 13

Patau Syndrome

Patau Syndrome

1:16,000 births, most stillborn but a few live to adulthood and are never independent in ADLs

Common phenotypes of trisomy 18

Most of trisomy 18 issues plus fusion of brain hemispheres, seizures, abnormal iris, close eyes, cleft palate, deafness, apnea, extra fingers and toes

What can occur if part of a chromosome is added or is missing?

Duplications or deletions

Duplications

extra copy of DNA amplifies gene expression

Deletions

missing DNA reduces gene expression

Why do duplications and deletions occur?

Random events, not linked to parental age

Retinoblastoma

tumors in retina due to deletion of RB gene on 13qdel(q12.2-q14.3)

RB gene

a tumor suppressor gene, therefore lacking a copy of this gene increased cell division resulting in tumors

Cri du Chat

deletion on chromosome 5 (5p) that results in microcephaly, cleft palate, heart defects, severe intellectual deficiencies, and a cry that sounds like a cat

The larger deletion, the more..

severe the disorder

Angelman Syndrome

deletion of maternal chromosome 15 that results in developmental delays, reduced cognition, clumsy gait, hand flapping, enlarged face and broad chin

Prader-Willi Syndrome

deletion of paternal chromosome 15 resulting in short, small hands and feet, reduced cognition, scoliosis, micropenis, insatiable appetite, delayed or incomplete puberty

Angelman and Prader-Willi Syndrome are..

deletion of the SAME part of chromosome but different syndromes due to parent is was deleted from

Why does chromosome 15 matter so much?

Unknown, but something is different for Chromosome 15 between men and women

Genetic imprinting

maternal and paternal DNA is marked slightly differently to allow for better regulation through histone methylation

Mosaicism

2 or more karyotypes are consistently present in 1 person, with some normal and abnormal cells

With mosaicisim, distribution in tissues is _____, therefore?

uneven; phenotypes are highly variable

How might mosaicism occur?

due to errors in cell division that happen after fertilization, leading to an individual having two or more genetically different sets of cells

How does mosaicism affect the severity of a syndrome with a genetic origin?

can cause a spectrum of symptoms, ranging from none to severe, depending on the number and location of affected cells

What is a phenotype common in both Trisomy 18 and 13?

rocker bottom feet